Cytokinins are a class of phytohormones, signalling molecules specific to plants. They act as regulators of diverse physiological processes in complex signalling pathways. It is necessary for plants to continuously regulate cytokinin distribution among different organs, tissues, cells, and compartments. Such regulatory mechanisms include cytokinin biosynthesis, metabolic conversions and degradation, as well as cytokinin membrane transport. In our review, we aim to provide a thorough picture of the latter. We begin by summarizing cytokinin structures and physicochemical properties. Then, we revise the elementary thermodynamic and kinetic aspects of cytokinin membrane transport. Next, we review which membrane-bound carrier proteins and protein families recognize cytokinins as their substrates. Namely, we discuss the families of "equilibrative nucleoside transporters" and "purine permeases", which translocate diverse purine-related compounds, and proteins AtPUP14, AtABCG14, AtAZG1, and AtAZG2, which are specific to cytokinins. We also address long-distance cytokinin transport. Putting all these pieces together, we finally discuss cytokinin distribution as a net result of these processes, diverse in their physicochemical nature but acting together to promote plant fitness.

Department of Biochemistry Faculty of Science Charles University 128 00 Prague Czech Republic

The Czech Academy of Sciences Institute of Experimental Botany 165 02 Prague Czech Republic

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Schaller G.E., Bishopp A., Kieber J.J. The Yin-Yang of Hormones: Cytokinin and Auxin Interactions in Plant Development. Plant Cell. 2015;27:44–63. doi: 10.1105/tpc.114.133595. PubMed DOI PMC

Kieber J.J., Schaller G.E. Cytokinin Signaling in Plant Development. Development. 2018;145:dev149344. doi: 10.1242/dev.149344. PubMed DOI

Skalický V., Kubeš M., Napier R., Novák O. Auxins and Cytokinins—The Role of Subcellular Organization on Homeostasis. Int. J. Mol. Sci. 2018;19:3115. doi: 10.3390/ijms19103115. PubMed DOI PMC

Akiyoshi D.E., Klee H., Amasino R.M., Nester E.W., Gordon M.P. T-DNA of Agrobacterium Tumefaciens Encodes an Enzyme of Cytokinin Biosynthesis. Proc. Natl. Acad. Sci. USA. 1984;81:5994–5998. doi: 10.1073/pnas.81.19.5994. PubMed DOI PMC

Kieber J.J., Schaller G.E. Cytokinins. Arab. Book. 2014;12:e0168. doi: 10.1199/tab.0168. PubMed DOI PMC

Takei K., Yamaya T., Sakakibara H. Arabidopsis CYP735A1 and CYP735A2 Encode Cytokinin Hydroxylases That Catalyze the Biosynthesis of Trans-Zeatin. J. Biol. Chem. 2004;279:41866–41872. doi: 10.1074/jbc.M406337200. PubMed DOI

Lomin S.N., Krivosheev D.M., Steklov M.Y., Arkhipov D.V., Osolodkin D.I., Schmülling T., Romanov G.A. Plant Membrane Assays with Cytokinin Receptors Underpin the Unique Role of Free Cytokinin Bases as Biologically Active Ligands. J. Exp. Bot. 2015;66:1851–1863. doi: 10.1093/jxb/eru522. PubMed DOI PMC

Chen C.-M., Kristopeit S.M. Metabolism of Cytokinin: Dephosphorylation of Cytokinin Ribonucleotide by 5′-Nucleotidases from Wheat Germ Cytosol. Plant Physiol. 1981;67:494–498. doi: 10.1104/pp.67.3.494. PubMed DOI PMC

Chen C.-M., Kristopeit S.M. Metabolism of Cytokinin: Deribosylation of Cytokinin Ribonucleoside by Adenosine Nucleosidase from Wheat Germ Cells. Plant Physiol. 1981;68:1020–1023. doi: 10.1104/pp.68.5.1020. PubMed DOI PMC

Kurakawa T., Ueda N., Maekawa M., Kobayashi K., Kojima M., Nagato Y., Sakakibara H., Kyozuka J. Direct Control of Shoot Meristem Activity by a Cytokinin-Activating Enzyme. Nature. 2007;445:652–655. doi: 10.1038/nature05504. PubMed DOI

Kuroha T., Tokunaga H., Kojima M., Ueda N., Ishida T., Nagawa S., Fukuda H., Sugimoto K., Sakakibara H. Functional Analyses of LONELY GUY Cytokinin-Activating Enzymes Reveal the Importance of the Direct Activation Pathway in Arabidopsis. Plant Cell. 2009;21:3152–3169. doi: 10.1105/tpc.109.068676. PubMed DOI PMC

Tokunaga H., Kojima M., Kuroha T., Ishida T., Sugimoto K., Kiba T., Sakakibara H. Arabidopsis Lonely Guy (LOG) Multiple Mutants Reveal a Central Role of the LOG-Dependent Pathway in Cytokinin Activation. Plant J. 2012;69:355–365. doi: 10.1111/j.1365-313X.2011.04795.x. PubMed DOI

Galuszka P., Frébort I., Šebela M., Sauer P., Jacobsen S., Peč P. Cytokinin Oxidase or Dehydrogenase? Eur. J. Biochem. 2001;268:450–461. doi: 10.1046/j.1432-1033.2001.01910.x. PubMed DOI

Schmülling T., Werner T., Riefler M., Krupková E., Bartrina y Manns I. Structure and Function of Cytokinin Oxidase/Dehydrogenase Genes of Maize, Rice, Arabidopsis and Other Species. J. Plant Res. 2003;116:241–252. doi: 10.1007/s10265-003-0096-4. PubMed DOI

Hou B., Lim E.-K., Higgins G.S., Bowles D.J. N-Glucosylation of Cytokinins by Glycosyltransferases of Arabidopsis Thaliana. J. Biol. Chem. 2004;279:47822–47832. doi: 10.1074/jbc.M409569200. PubMed DOI

Brzobohatý B., Moore I., Kristoffersen P., Bako L., Campos N., Schell J., Palme K. Release of Active Cytokinin by a Beta-Glucosidase Localized to the Maize Root Meristem. Science. 1993;262:1051–1054. doi: 10.1126/science.8235622. PubMed DOI

Hošek P., Hoyerová K., Kiran N.S., Dobrev P.I., Zahajská L., Filepová R., Motyka V., Müller K., Kamínek M. Distinct Metabolism of N-Glucosides of Isopentenyladenine and Trans-Zeatin Determines Cytokinin Metabolic Spectrum in Arabidopsis. New Phytol. 2020;225:2423–2438. doi: 10.1111/nph.16310. PubMed DOI

Vylíčilová H., Bryksová M., Matušková V., Doležal K., Plíhalová L., Strnad M. Naturally Occurring and Artificial N9-Cytokinin Conjugates: From Synthesis to Biological Activity and Back. Biomolecules. 2020;10:832. doi: 10.3390/biom10060832. PubMed DOI PMC

Romanov G.A., Lomin S.N., Schmülling T. Cytokinin Signaling: From the ER or from the PM? That is the Question! New Phytol. 2018;218:41–53. doi: 10.1111/nph.14991. PubMed DOI

Inoue T., Higuchi M., Hashimoto Y., Seki M., Kobayashi M., Kato T., Tabata S., Shinozaki K., Kakimoto T. Identification of CRE1 as a Cytokinin Receptor from Arabidopsis. Nature. 2001;409:1060–1063. doi: 10.1038/35059117. PubMed DOI

Ueguchi C., Koizumi H., Suzuki T., Mizuno T. Novel Family of Sensor Histidine Kinase Genes in Arabidopsis Thaliana. Plant Cell Physiol. 2001;42:231–235. doi: 10.1093/pcp/pce015. PubMed DOI

Kim H.J., Ryu H., Hong S.H., Woo H.R., Lim P.O., Lee I.C., Sheen J., Nam H.G., Hwang I. Cytokinin-Mediated Control of Leaf Longevity by AHK3 through Phosphorylation of ARR2 in Arabidopsis. Proc. Natl. Acad. Sci. USA. 2006;103:814–819. doi: 10.1073/pnas.0505150103. PubMed DOI PMC

Caesar K., Thamm A.M.K., Witthöft J., Elgass K., Huppenberger P., Grefen C., Horak J., Harter K. Evidence for the Localization of the Arabidopsis Cytokinin Receptors AHK3 and AHK4 in the Endoplasmic Reticulum. J. Exp. Bot. 2011;62:5571–5580. doi: 10.1093/jxb/err238. PubMed DOI PMC

Wulfetange K., Lomin S.N., Romanov G.A., Stolz A., Heyl A., Schmülling T. The Cytokinin Receptors of Arabidopsis are Located Mainly to the Endoplasmic Reticulum. Plant Physiol. 2011;156:1808–1818. doi: 10.1104/pp.111.180539. PubMed DOI PMC

Lomin S.N., Myakushina Y.A., Arkhipov D.V., Leonova O.G., Popenko V.I., Schmülling T., Romanov G.A. Studies of Cytokinin Receptor-Phosphotransmitter Interaction Provide Evidences for the Initiation of Cytokinin Signalling in the Endoplasmic Reticulum. Funct. Plant Biol. 2018;45:192–202. doi: 10.1071/FP16292. PubMed DOI

Antoniadi I., Novák O., Gelová Z., Johnson A., Plíhal O., Simerský R., Mik V., Vain T., Mateo-Bonmatí E., Karady M., et al. Cell-Surface Receptors Enable Perception of Extracellular Cytokinins. Nat. Commun. 2020;11:4284. doi: 10.1038/s41467-020-17700-9. PubMed DOI PMC

Kubiasová K., Montesinos J.C., Šamajová O., Nisler J., Mik V., Semerádová H., Plíhalová L., Novák O., Marhavý P., Cavallari N., et al. Cytokinin Fluoroprobe Reveals Multiple Sites of Cytokinin Perception at Plasma Membrane and Endoplasmic Reticulum. Nat. Commun. 2020;11:4285. doi: 10.1038/s41467-020-17949-0. PubMed DOI PMC

Zürcher E., Liu J., di Donato M., Geisler M., Müller B. Plant Development Regulated by Cytokinin Sinks. Science. 2016;353:1027–1030. doi: 10.1126/science.aaf7254. PubMed DOI

Hluska T., Hlusková L., Emery R.J. The Hulks and the Deadpools of the Cytokinin Universe: A Dual Strategy for Cytokinin Production, Translocation, and Signal Transduction. Biomolecules. 2021;11:209. doi: 10.3390/biom11020209. PubMed DOI PMC

Kieber J.J. Cytokinins: Regulators of Cell Division. In: Taiz L., Zeiger E., editors. Plant Physiology. Sinauer Associates, Inc.; Sunderland, MA, USA: 2002. pp. 493–517.

Spíchal L. Cytokinins—Recent News and Views of Evolutionally Old Molecules. Funct. Plant Biol. 2012;39:267–284. doi: 10.1071/FP11276. PubMed DOI

Nedvěd D. Master’s Thesis. Charles University; Prague, Czech Republic: 2020. Transport and Metabolism of Radio-Labelled Cytokinins in Plant Cells and Tissues.

Vickers C.E., Bongers M., Liu Q., Delatte T., Bouwmeester H. Metabolic Engineering of Volatile Isoprenoids in Plants and Microbes. Plant Cell Environ. 2014;37:1753–1775. doi: 10.1111/pce.12316. PubMed DOI

Gajdošová S., Spíchal L., Kamínek M., Hoyerová K., Novák O., Dobrev P.I., Galuszka P., Klíma P., Gaudinová A., Žižková E., et al. Distribution, Biological Activities, Metabolism, and the Conceivable Function of Cis-Zeatin-Type Cytokinins in Plants. J. Exp. Bot. 2011;62:2827–2840. doi: 10.1093/jxb/erq457. PubMed DOI

Heyl A., Riefler M., Romanov G.A., Schmülling T. Properties, Functions and Evolution of Cytokinin Receptors. Eur. J. Cell Biol. 2012;91:246–256. doi: 10.1016/j.ejcb.2011.02.009. PubMed DOI

Bassil N.V., Mok D.W.S., Mok M.C. Partial Purification of a Cis-Trans-Isomerase of Zeatin from Immature Seed of Phaseolus Vulgaris L. Plant Physiol. 1993;102:867–872. doi: 10.1104/pp.102.3.867. PubMed DOI PMC

Hluska T., Šebela M., Lenobel R., Frébort I., Galuszka P. Purification of Maize Nucleotide Pyrophosphatase/Phosphodiesterase Casts Doubt on the Existence of Zeatin Cis–Trans Isomerase in Plants. Front. Plant Sci. 2017;8 doi: 10.3389/fpls.2017.01473. PubMed DOI PMC

Miyawaki K., Tarkowski P., Matsumoto-Kitano M., Kato T., Sato S., Tarkowska D., Tabata S., Sandberg G., Kakimoto T. Roles of Arabidopsis ATP/ADP Isopentenyltransferases and TRNA Isopentenyltransferases in Cytokinin Biosynthesis. Proc. Natl. Acad. Sci. USA. 2006;103:16598–16603. doi: 10.1073/pnas.0603522103. PubMed DOI PMC

Martin R.C., Mok M.C., Shaw G., Mok D.W.S. An Enzyme Mediating the Conversion of Zeatin to Dihydrozeatin in Phaseolus Embryos. Plant Physiol. 1989;90:1630–1635. doi: 10.1104/pp.90.4.1630. PubMed DOI PMC

Gaudinová A., Dobrev P.I., Šolcová B., Novák O., Strnad M., Friedecký D., Motyka V. The Involvement of Cytokinin Oxidase/Dehydrogenase and Zeatin Reductase in Regulation of Cytokinin Levels in Pea (Pisum Sativum L.) Leaves. J. Plant Growth Regul. 2005;24:188–200. doi: 10.1007/s00344-005-0043-9. DOI

Kolachevskaya O.O., Sergeeva L.I., Floková K., Getman I.A., Lomin S.N., Alekseeva V.V., Rukavtsova E.B., Buryanov Y.I., Romanov G.A. Auxin Synthesis Gene Tms1 Driven by Tuber-Specific Promoter Alters Hormonal Status of Transgenic Potato Plants and Their Responses to Exogenous Phytohormones. Plant Cell Rep. 2017;36:419–435. doi: 10.1007/s00299-016-2091-y. PubMed DOI

Tarkowská D., Doležal K., Tarkowski P., Åstot C., Holub J., Fuksová K., Schmülling T., Sandberg G., Strnad M. Identification of New Aromatic Cytokinins in Arabidopsis Thaliana and Populus × Canadensis Leaves by LC-(+)ESI-MS and Capillary Liquid Chromatography/Frit–Fast Atom Bombardment Mass Spectrometry. Physiol. Plant. 2003;117:579–590. doi: 10.1034/j.1399-3054.2003.00071.x. PubMed DOI

Strnad M. The Aromatic Cytokinins. Physiol. Plant. 1997;101:674–688. doi: 10.1111/j.1399-3054.1997.tb01052.x. DOI

Hluska T., Dobrev P.I., Tarkowská D., Frébortová J., Zalabák D., Kopečný D., Plíhal O., Kokáš F., Briozzo P., Zatloukal M., et al. Cytokinin Metabolism in Maize: Novel Evidence of Cytokinin Abundance, Interconversions and Formation of a New Trans-Zeatin Metabolic Product with a Weak Anticytokinin Activity. Plant Sci. 2016;247:127–137. doi: 10.1016/j.plantsci.2016.03.014. PubMed DOI

Sørensen J.L., Benfield A.H., Wollenberg R.D., Westphal K., Wimmer R., Nielsen M.R., Nielsen K.F., Carere J., Covarelli L., Beccari G., et al. The Cereal Pathogen Fusarium Pseudograminearum Produces a New Class of Active Cytokinins during Infection. Mol. Plant Pathol. 2017;19:1140–1154. doi: 10.1111/mpp.12593. PubMed DOI PMC

Haidoune M., Mornet R., Laloue M. Synthesis of 6-(3-Methylpyrrol-1-Yl)-9-β-D-Ribofuranosyl Purine, a Novel Metabolite of Zeatin Riboside. Tetrahedron Lett. 1990;31:1419–1422. doi: 10.1016/S0040-4039(00)88821-8. DOI

Mok M.C., Martin R.C., Dobrev P.I., Vanková R., Ho P.S., Yonekura-Sakakibara K., Sakakibara H., Mok D.W.S. Topolins and Hydroxylated Thidiazuron Derivatives are Substrates of Cytokinin O-Glucosyltransferase with Position Specificity Related to Receptor Recognition. Plant Physiol. 2005;137:1057–1066. doi: 10.1104/pp.104.057174. PubMed DOI PMC

Galuszka P., Popelková H., Werner T., Frébortová J., Pospíšilová H., Mik V., Köllmer I., Schmülling T., Frébort I. Biochemical Characterization of Cytokinin Oxidases/Dehydrogenases from Arabidopsis Thaliana Expressed in Nicotiana Tabacum L. J. Plant Growth Regul. 2007;26:255–267. doi: 10.1007/s00344-007-9008-5. DOI

Evidente A., Fujii T., Iacobellis N.S., Riva S., Sisto A., Surico G. Structure-Activity Relationships of Zeatin Cytokinins Produced by Plant PathogenicPseudomonades. Phytochemistry. 1991;30:3505–3510. doi: 10.1016/0031-9422(91)80055-6. DOI

Pertry I., Václavíková K., Depuydt S., Galuszka P., Spíchal L., Temmerman W., Stes E., Schmülling T., Kakimoto T., Montagu M.C.E.V., et al. Identification of Rhodococcus Fascians Cytokinins and Their Modus Operandi to Reshape the Plant. Proc. Natl. Acad. Sci. USA. 2009;106:929–934. doi: 10.1073/pnas.0811683106. PubMed DOI PMC

Radhika V., Ueda N., Tsuboi Y., Kojima M., Kikuchi J., Kudo T., Sakakibara H. Methylated Cytokinins from the Phytopathogen Rhodococcus Fascians Mimic Plant Hormone Activity. Plant Physiol. 2015;169:1118–1126. doi: 10.1104/pp.15.00787. PubMed DOI PMC

Gibb M., Kisiala A.B., Morrison E.N., Emery R.J.N. The Origins and Roles of Methylthiolated Cytokinins: Evidence from Among Life Kingdoms. Front. Cell Dev. Biol. 2020;8:605672. doi: 10.3389/fcell.2020.605672. PubMed DOI PMC

Oshchepkov M.S., Kalistratova A.V., Savelieva E.M., Romanov G.A., Bystrova N.A., Kochetkov K.A. Natural and Synthetic Cytokinins and Their Applications in Biotechnology, Agrochemistry and Medicine. Russ. Chem. Rev. 2020;89:787. doi: 10.1070/RCR4921. DOI

Wildman S.A., Crippen G.M. Prediction of Physicochemical Parameters by Atomic Contributions. J. Chem. Inf. Comput. Sci. 1999;39:868–873. doi: 10.1021/ci990307l. DOI

Šimura J., Antoniadi I., Široká J., Tarkowská D., Strnad M., Ljung K., Novák O. Plant Hormonomics: Multiple Phytohormone Profiling by Targeted Metabolomics. Plant Physiol. 2018;177:476–489. doi: 10.1104/pp.18.00293. PubMed DOI PMC

Buchanan B.B., Gruissem W., Jones R.L., editors. Biochemistry & Molecular Biology of Plants. 2nd ed. Wiley-Blackwell; Hoboken, NJ, USA: 2015.

Chen W., Gai Y., Liu S., Wang R., Jiang X. Quantitative Analysis of Cytokinins in Plants by High Performance Liquid Chromatography: Electronspray Ionization Ion Trap Mass Spectrometry. J. Integr. Plant Biol. 2010;52:925–932. doi: 10.1111/j.1744-7909.2010.00989.x. PubMed DOI

Dobrev P.I., Hoyerová K., Petrášek J. Analytical Determination of Auxins and Cytokinins. In: Dandekar T., Naseem M., editors. Auxins and Cytokinins in Plant Biology. Volume 1569. Methods in Molecular Biology; Springer; New York, NY, USA: 2017. pp. 31–39. PubMed

Hoyerová K., Gaudinová A., Malbeck J., Dobrev P.I., Kocábek T., Šolcová B., Trávníčková A., Kamínek M. Efficiency of Different Methods of Extraction and Purification of Cytokinins. Phytochemistry. 2006;67:1151–1159. doi: 10.1016/j.phytochem.2006.03.010. PubMed DOI

Gillissen B., Bürkle L., André B., Kühn C., Rentsch D., Brandl B., Frommer W.B. A New Family of High-Affinity Transporters for Adenine, Cytosine, and Purine Derivatives in Arabidopsis. Plant Cell. 2000;12:291–300. doi: 10.1105/tpc.12.2.291. PubMed DOI PMC

Bürkle L., Cedzich A., Döpke C., Stransky H., Okumoto S., Gillissen B., Kühn C., Frommer W.B. Transport of Cytokinins Mediated by Purine Transporters of the PUP Family Expressed in Phloem, Hydathodes, and Pollen of Arabidopsis. Plant J. 2003;34:13–26. doi: 10.1046/j.1365-313X.2003.01700.x. PubMed DOI

Sun J., Hirose N., Wang X., Wen P., Xue L., Sakakibara H., Zuo J. Arabidopsis SOI33/AtENT8 Gene Encodes a Putative Equilibrative Nucleoside Transporter That is Involved in Cytokinin Transport In Planta. J. Integr. Plant Biol. 2005;47:588–603. doi: 10.1111/j.1744-7909.2005.00104.x. DOI

Spíchal L., Rakova N.Y., Riefler M., Mizuno T., Romanov G.A., Strnad M., Schmülling T. Two Cytokinin Receptors of Arabidopsis Thaliana, CRE1/AHK4 and AHK3, Differ in Their Ligand Specificity in a Bacterial Assay. Plant Cell Physiol. 2004;45:1299–1305. doi: 10.1093/pcp/pch132. PubMed DOI

Yonekura-Sakakibara K., Kojima M., Yamaya T., Sakakibara H. Molecular Characterization of Cytokinin-Responsive Histidine Kinases in Maize. Differential Ligand Preferences and Response to Cis-Zeatin. Plant Physiol. 2004;134:1654–1661. doi: 10.1104/pp.103.037176. PubMed DOI PMC

Lomin S.N., Krivosheev D.M., Steklov M.Y., Osolodkin D.I., Romanov G.A. Receptor Properties and Features of Cytokinin Signaling. Acta Nat. 2012;4:31–45. doi: 10.32607/20758251-2012-4-3-31-45. PubMed DOI PMC

Hirose N., Makita N., Yamaya T., Sakakibara H. Functional Characterization and Expression Analysis of a Gene, OsENT2, Encoding an Equilibrative Nucleoside Transporter in Rice Suggest a Function in Cytokinin Transport. Plant Physiol. 2005;138:196–206. doi: 10.1104/pp.105.060137. PubMed DOI PMC

Hirose N., Takei K., Kuroha T., Kamada-Nobusada T., Hayashi H., Sakakibara H. Regulation of Cytokinin Biosynthesis, Compartmentalization and Translocation. J. Exp. Bot. 2008;59:75–83. doi: 10.1093/jxb/erm157. PubMed DOI

Qi Z., Xiong L. Characterization of a Purine Permease Family Gene OsPUP7 Involved in Growth and Development Control in Rice. J. Integr. Plant Biol. 2013;55:1119–1135. doi: 10.1111/jipb.12101. PubMed DOI

Dobrev P.I., Kamínek M. Fast and Efficient Separation of Cytokinins from Auxin and Abscisic Acid and Their Purification Using Mixed-Mode Solid-Phase Extraction. J. Chromatogr. A. 2002;950:21–29. doi: 10.1016/S0021-9673(02)00024-9. PubMed DOI

Jiskrová E., Novák O., Pospíšilová H., Holubová K., Karády M., Galuszka P., Robert S., Frébort I. Extra- and Intracellular Distribution of Cytokinins in the Leaves of Monocots and Dicots. New Biotechnol. 2016;33:735–742. doi: 10.1016/j.nbt.2015.12.010. PubMed DOI

Beveridge C.A., Murfet I.C., Kerhoas L., Sotta B., Miginiac E., Rameau C. The Shoot Controls Zeatin Riboside Export from Pea Roots. Evidence from the Branching Mutant Rms4. Plant J. 1997;11:339–345. doi: 10.1046/j.1365-313X.1997.11020339.x. DOI

Kuroha T., Kato H., Asami T., Yoshida S., Kamada H., Satoh S. A Trans-zeatin Riboside in Root Xylem Sap Negatively Regulates Adventitious Root Formation on Cucumber Hypocotyls. J. Exp. Bot. 2002;53:2193–2200. doi: 10.1093/jxb/erf077. PubMed DOI

Takei K., Sakakibara H., Taniguchi M., Sugiyama T. Nitrogen-Dependent Accumulation of Cytokinins in Root and TheTranslocation to Leaf: Implication of Cytokinin Species That Induces GeneExpression of Maize ResponseRegulator. Plant Cell Physiol. 2001;42:85–93. doi: 10.1093/pcp/pce009. PubMed DOI

Corbesier L., Prinsen E., Jacqmard A., Lejeune P., van Onckelen H., Périlleux C., Bernier G. Cytokinin Levels in Leaves, Leaf Exudate and Shoot Apical Meristem of Arabidopsis Thaliana during Floral Transition. J. Exp. Bot. 2003;54:2511–2517. doi: 10.1093/jxb/erg276. PubMed DOI

Jin S.-H., Ma X.-M., Kojima M., Sakakibara H., Wang Y.-W., Hou B.-K. Overexpression of Glucosyltransferase UGT85A1 Influences Trans-Zeatin Homeostasis and Trans-Zeatin Responses Likely through O-Glucosylation. Planta. 2013;237:991–999. doi: 10.1007/s00425-012-1818-4. PubMed DOI

Šmehilová M., Dobrůšková J., Novák O., Takáč T., Galuszka P. Cytokinin-Specific Glycosyltransferases Possess Different Roles in Cytokinin Homeostasis Maintenance. Front. Plant Sci. 2016;7 doi: 10.3389/fpls.2016.01264. PubMed DOI PMC

Benková E., Witters E., Dongen W.V., Kolar J., Motyka V., Brzobohatý B., Onckelen H.A.V., Machácková I. Cytokinins in Tobacco and Wheat Chloroplasts. Occurrence and Changes Due to Light/Dark Treatment. Plant Physiol. 1999;121:245–252. doi: 10.1104/pp.121.1.245. PubMed DOI PMC

Galbraith D., Loureiro J., Antoniadi I., Bainard J., Bureš P., Cápal P., Castro M., Castro S., Čertner M., Čertnerová D., et al. Best Practices in Plant Cytometry. Cytom. Part. A. 2021:1–7. doi: 10.1002/cyto.a.24295. PubMed DOI

Wilkens S. Structure and Mechanism of ABC Transporters. F1000Prime Rep. 2015;7 doi: 10.12703/P7-14. PubMed DOI PMC

Kang J., Park J., Choi H., Burla B., Kretzschmar T., Lee Y., Martinoia E. Plant ABC Transporters. Arab. Book. 2011;9 doi: 10.1199/tab.0153. PubMed DOI PMC

Girke C., Daumann M., Niopek-Witz S., Möhlmann T. Nucleobase and Nucleoside Transport and Integration into Plant Metabolism. Front. Plant Sci. 2014;5 doi: 10.3389/fpls.2014.00443. PubMed DOI PMC

Paul A., Laurila T., Vuorinen V., Divinski S.V. Fick’s Laws of Diffusion. In: Paul A., Laurila T., Vuorinen V., Divinski S.V., editors. Thermodynamics, Diffusion and the Kirkendall Effect in Solids. Springer International Publishing; Cham, Switzerland: 2014. pp. 115–139.

El-Showk S., Help-Rinta-Rahko H., Blomster T., Siligato R., Marée A.F.M., Mähönen A.P., Grieneisen V.A. Parsimonious Model of Vascular Patterning Links Transverse Hormone Fluxes to Lateral Root Initiation: Auxin Leads the Way, While Cytokinin Levels Out. PLoS Comput. Biol. 2015;11:e1004450. doi: 10.1371/journal.pcbi.1004450. PubMed DOI PMC

Hošek P., Kubeš M., Laňková M., Dobrev P.I., Klíma P., Kohoutová M., Petrášek J., Hoyerová K., Jiřina M., Zažímalová E. Auxin Transport at Cellular Level: New Insights Supported by Mathematical Modelling. J. Exp. Bot. 2012;63:3815–3827. doi: 10.1093/jxb/ers074. PubMed DOI PMC

Moore S., Zhang X., Mudge A., Rowe J.H., Topping J.F., Liu J., Lindsey K. Spatiotemporal Modelling of Hormonal Crosstalk Explains the Level and Patterning of Hormones and Gene Expression in Arabidopsis Thaliana Wild-Type and Mutant Roots. New Phytol. 2015;207:1110–1122. doi: 10.1111/nph.13421. PubMed DOI PMC

Zažímalová E., Murphy A.S., Yang H., Hoyerová K., Hošek P. Auxin Transporters—Why So Many? Cold Spring Harb. Perspect. Biol. 2010;2:a001552. doi: 10.1101/cshperspect.a001552. PubMed DOI PMC

Kramer E.M. How Far Can a Molecule of Weak Acid Travel in the Apoplast or Xylem? Plant Physiol. 2006;141:1233–1236. doi: 10.1104/pp.106.083790. PubMed DOI PMC

Wormit A., Traub M., Flörchinger M., Neuhaus H.E., Möhlmann T. Characterization of Three Novel Members of the Arabidopsis Thaliana Equilibrative Nucleoside Transporter (ENT) Family. Biochem. J. 2004;383:19–26. doi: 10.1042/BJ20040389. PubMed DOI PMC

Michaelis L., Menten M.L. Die Kinetik Der Invertinwirkung. Biochemische Zeitschrift. 1913;49:333–369.

Johnson K.A., Goody R.S. The Original Michaelis Constant: Translation of the 1913 Michaelis-Menten Paper. Biochemistry. 2011;50:8264–8269. doi: 10.1021/bi201284u. PubMed DOI PMC

Li J., Wang D. Cloning and in Vitro Expression of the CDNA Encoding a Putative Nucleoside Transporter from Arabidopsis Thaliana. Plant Sci. 2000;157:23–32. doi: 10.1016/S0168-9452(00)00261-2. PubMed DOI

Möhlmann T., Mezher Z., Schwerdtfeger G., Neuhaus H.E. Characterisation of a Concentrative Type of Adenosine Transporter from Arabidopsis Thaliana (ENT1,At) FEBS Lett. 2001;509:370–374. doi: 10.1016/S0014-5793(01)03195-7. PubMed DOI

Bernard C., Traub M., Kunz H.-H., Hach S., Trentmann O., Möhlmann T. Equilibrative Nucleoside Transporter 1 (ENT1) is Critical for Pollen Germination and Vegetative Growth in Arabidopsis. J. Exp. Bot. 2011;62:4627–4637. doi: 10.1093/jxb/err183. PubMed DOI PMC

Girke C., Arutyunova E., Syed M., Traub M., Möhlmann T., Lemieux M.J. High Yield Expression and Purification of Equilibrative Nucleoside Transporter 7 (ENT7) from Arabidopsis Thaliana. Biochim. Biophys. Acta BBA Gen. Subj. 2015;1850:1921–1929. doi: 10.1016/j.bbagen.2015.06.003. PubMed DOI

Li G., Liu K., Baldwin S.A., Wang D. Equilibrative Nucleoside Transporters of Arabidopsis Thaliana: CDNA Cloning, Expression Pattern, and Analysis of Transport Activities. J. Biol. Chem. 2003;278:35732–35742. doi: 10.1074/jbc.M304768200. PubMed DOI

Traub M., Flörchinger M., Piecuch J., Kunz H., Weise-Steinmetz A., Deitmer Joachim W., Ekkehard Neuhaus H., Möhlmann T. The Fluorouridine Insensitive 1 (Fur1) Mutant is Defective in Equilibrative Nucleoside Transporter 3 (ENT3), and Thus Represents an Important Pyrimidine Nucleoside Uptake System in Arabidopsis Thaliana. Plant J. 2007;49:855–864. doi: 10.1111/j.1365-313X.2006.02998.x. PubMed DOI

Boswell-Casteel R.C., Hays F.A. Equilibrative Nucleoside Transporters—A Review. Nucleosides Nucleotides Nucleic Acids. 2017;36:7–30. doi: 10.1080/15257770.2016.1210805. PubMed DOI PMC

Young J.D., Yao S.Y.M., Baldwin J.M., Cass C.E., Baldwin S.A. The Human Concentrative and Equilibrative Nucleoside Transporter Families, SLC28 and SLC29. Mol. Asp. Med. 2013;34:529–547. doi: 10.1016/j.mam.2012.05.007. PubMed DOI

Hildreth S.B., Gehman E.A., Yang H., Lu R.-H., Ritech C.K., Harich K.C., Yu S., Lin J., Sandoe J.L., Okumoto S., et al. Tobacco Nicotine Uptake Permease (NUP1) Affects Alkaloid Metabolism. Proc. Natl. Acad. Sci. USA. 2011;108:18179–18184. doi: 10.1073/pnas.1108620108. PubMed DOI PMC

Cedzich A., Stransky H., Schulz B., Frommer W.B. Characterization of Cytokinin and Adenine Transport in Arabidopsis Cell Cultures. Plant Physiol. 2008;148:1857–1867. doi: 10.1104/pp.108.128454. PubMed DOI PMC

Durán-Medina Y., Díaz-Ramírez D., Marsch-Martínez N. Cytokinins on the Move. Front. Plant Sci. 2017;8 doi: 10.3389/fpls.2017.00146. PubMed DOI PMC

Liu C.-J., Zhao Y., Zhang K. Cytokinin Transporters: Multisite Players in Cytokinin Homeostasis and Signal Distribution. Front. Plant Sci. 2019;10 doi: 10.3389/fpls.2019.00693. PubMed DOI PMC

Szydlowski N., Bürkle L., Pourcel L., Moulin M., Stolz J., Fitzpatrick T.B. Recycling of Pyridoxine (Vitamin B6) by PUP1 in Arabidopsis. Plant J. 2013;75:40–52. doi: 10.1111/tpj.12195. PubMed DOI

Xiao Y., Liu D., Zhang G., Gao S., Liu L., Xu F., Che R., Wang Y., Tong H., Chu C. Big Grain3, Encoding a Purine Permease, Regulates Grain Size via Modulating Cytokinin Transport in Rice. J. Integr. Plant Biol. 2019;61:581–597. doi: 10.1111/jipb.12727. PubMed DOI

Xiao Y., Zhang J., Yu G., Lu X., Mei W., Deng H., Zhang G., Chen G., Chu C., Tong H., et al. Endoplasmic Reticulum-Localized PURINE PERMEASE1 Regulates Plant Height and Grain Weight by Modulating Cytokinin Distribution in Rice. Front. Plant Sci. 2020;11 doi: 10.3389/fpls.2020.618560. PubMed DOI PMC

Zürcher E., Tavor-Deslex D., Lituiev D., Enkerli K., Tarr P.T., Müller B. A Robust and Sensitive Synthetic Sensor to Monitor the Transcriptional Output of the Cytokinin Signaling Network in Planta. Plant Physiol. 2013;161:1066–1075. doi: 10.1104/pp.112.211763. PubMed DOI PMC

Ko D., Kang J., Kiba T., Park J., Kojima M., Do J., Kim K.Y., Kwon M., Endler A., Song W.-Y., et al. Arabidopsis ABCG14 Is Essential for the Root-to-Shoot Translocation of Cytokinin. Proc. Natl. Acad. Sci. USA. 2014;111:7150–7155. doi: 10.1073/pnas.1321519111. PubMed DOI PMC

Le Hir R., Sorin C., Chakraborti D., Moritz T., Schaller H., Tellier F., Robert S., Morin H., Bako L., Bellini C. ABCG9, ABCG11 and ABCG14 ABC Transporters are Required for Vascular Development in Arabidopsis. Plant J. 2013;76:811–824. doi: 10.1111/tpj.12334. PubMed DOI

Zhang K., Novak O., Wei Z., Gou M., Zhang X., Yu Y., Yang H., Cai Y., Strnad M., Liu C.-J. Arabidopsis ABCG14 Protein Controls the Acropetal Translocation of Root-Synthesized Cytokinins. Nat. Commun. 2014;5:1–12. doi: 10.1038/ncomms4274. PubMed DOI

Zhao J., Yu N., Ju M., Fan B., Zhang Y., Zhu E., Zhang M., Zhang K. ABC Transporter OsABCG18 Controls the Shootward Transport of Cytokinins and Grain Yield in Rice. J. Exp. Bot. 2019;70:6277–6291. doi: 10.1093/jxb/erz382. PubMed DOI PMC

Mansfield T.A., Schultes N.P., Mourad G.S. AtAzg1 and AtAzg2 Comprise a Novel Family of Purine Transporters in Arabidopsis. FEBS Lett. 2009;583:481–486. doi: 10.1016/j.febslet.2008.12.048. PubMed DOI

Tessi T.M., Brumm S., Winklbauer E., Schumacher B., Pettinari G., Lescano I., González C.A., Wanke D., Maurino V.G., Harter K., et al. Arabidopsis AZG2 Transports Cytokinins in vivo and Regulates Lateral Root Emergence. New Phytol. 2020;229:979–993. doi: 10.1111/nph.16943. PubMed DOI

Tessi T.M., Shahriari M., Maurino V.G., Meissner E., Novak O., Pasternak T., Schumacher B.S., Flubacher N.S., Nautscher M., Williams A., et al. The Auxin Transporter PIN1 and the Cytokinin Transporter AZG1 Interact to Regulate the Root Stress Response. bioRxiv. 2020 doi: 10.1101/2020.10.22.350363. DOI

Faiss M., Zalubilová J., Strnad M., Schmülling T. Conditional Transgenic Expression of the Ipt Gene Indicates a Function for Cytokinins in Paracrine Signaling in Whole Tobacco Plants. Plant J. 1997;12:401–415. doi: 10.1046/j.1365-313X.1997.12020401.x. PubMed DOI

De Rybel B., Adibi M., Breda A.S., Wendrich J.R., Smit M.E., Novák O., Yamaguchi N., Yoshida S., Isterdael G.V., Palovaara J., et al. Integration of Growth and Patterning during Vascular Tissue Formation in Arabidopsis. Science. 2014;345 doi: 10.1126/science.1255215. PubMed DOI

Badenoch-Jones J., Letham D.S., Parker C.W., Rolfe B.G. Quantitation of Cytokinins in Biological Samples Using Antibodies Against Zeatin Riboside. Plant Physiol. 1984;75:1117–1125. doi: 10.1104/pp.75.4.1117. PubMed DOI PMC

Abo-Hamed S., Collin H.A., Hardwick K. Biochemical and Physiological Aspects of Leaf Development in Cocoa (Theobroma Cacao L.) New Phytol. 1984;97:219–225. doi: 10.1111/j.1469-8137.1984.tb04125.x. DOI

Kudoyarova G.R., Korobova A.V., Akhiyarova G.R., Arkhipova T.N., Zaytsev D.Y., Prinsen E., Egutkin N.L., Medvedev S.S., Veselov S.Y. Accumulation of Cytokinins in Roots and Their Export to the Shoots of Durum Wheat Plants Treated with the Protonophore Carbonyl Cyanide M-Chlorophenylhydrazone (CCCP) J. Exp. Bot. 2014;65:2287–2294. doi: 10.1093/jxb/eru113. PubMed DOI PMC

Osugi A., Kojima M., Takebayashi Y., Ueda N., Kiba T., Sakakibara H. Systemic Transport of Trans-Zeatin and Its Precursor Have Differing Roles in Arabidopsis Shoots. Nat. Plants. 2017;3:17112. doi: 10.1038/nplants.2017.112. PubMed DOI

Matsumoto-Kitano M., Kusumoto T., Tarkowski P., Kinoshita-Tsujimura K., Václavíková K., Miyawaki K., Kakimoto T. Cytokinins are Central Regulators of Cambial Activity. Proc. Natl. Acad. Sci. USA. 2008;105:20027–20031. doi: 10.1073/pnas.0805619105. PubMed DOI PMC

Integrating the Roles for Cytokinin and Auxin in De Novo Shoot Organogenesis: From Hormone Uptake to Signaling Outputs