The efficacy of current antimalarial drugs is threatened by reduced susceptibility of Plasmodium falciparum to artemisinin, associated with mutations in pfkelch13 Another gene with variants known to modulate the response to artemisinin encodes the μ subunit of the AP-2 adaptin trafficking complex. To elucidate the cellular role of AP-2μ in P. falciparum, we performed a conditional gene knockout, which severely disrupted schizont organization and maturation, leading to mislocalization of key merozoite proteins. AP-2μ is thus essential for blood-stage replication. We generated transgenic P. falciparum parasites expressing hemagglutinin-tagged AP-2μ and examined cellular localization by fluorescence and electron microscopy. Together with mass spectrometry analysis of coimmunoprecipitating proteins, these studies identified AP-2μ-interacting partners, including other AP-2 subunits, the K10 kelch-domain protein, and PfEHD, an effector of endocytosis and lipid mobilization, but no evidence was found of interaction with clathrin, the expected coat protein for AP-2 vesicles. In reverse immunoprecipitation experiments with a clathrin nanobody, other heterotetrameric AP-complexes were shown to interact with clathrin, but AP-2 complex subunits were absent.IMPORTANCE We examine in detail the AP-2 adaptin complex from the malaria parasite Plasmodium falciparum In most studied organisms, AP-2 is involved in bringing material into the cell from outside, a process called endocytosis. Previous work shows that changes to the μ subunit of AP-2 can contribute to drug resistance. Our experiments show that AP-2 is essential for parasite development in blood but does not have any role in clathrin-mediated endocytosis. This suggests that a specialized function for AP-2 has developed in malaria parasites, and this may be important for understanding its impact on drug resistance.

• Klíčová slova
• Plasmodium falciparum, adaptin trafficking complex, adaptor proteins, artemisinin susceptibility, endocytosis, malaria,
• MeSH
• adaptorový proteinový komplex 2 genetika   metabolismus   MeSH
• antimalarika farmakologie   MeSH
• artemisininy metabolismus   MeSH
• endocytóza fyziologie   MeSH
• geneticky modifikované organismy MeSH
• genový knockout MeSH
• klathrin metabolismus   MeSH
• léková rezistence MeSH
• membránové proteiny metabolismus   MeSH
• Plasmodium falciparum účinky léků   genetika   metabolismus   MeSH
• protozoální proteiny genetika   metabolismus   MeSH
• schizonti účinky léků   genetika   metabolismus   MeSH
• transport proteinů MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• adaptorový proteinový komplex 2 MeSH
• antimalarika MeSH
• artemisinin MeSH Prohlížeč
• artemisininy MeSH
• klathrin MeSH
• membránové proteiny MeSH
• protozoální proteiny MeSH

Stilbenoids represent a large group of bioactive compounds, which occur in food and medicinal plants. Twenty-five stilbenoids were screened in vitro for their ability to inhibit COX-1, COX-2 and 5-LOX. Piceatannol and pinostilbene showed activity comparable to the zileuton and ibuprofen, respectively. The anti-inflammatory potential of stilbenoids was further evaluated using THP-1 human monocytic leukemia cell line. Tests of the cytotoxicity on the THP-1 and HCT116 cell lines showed very low toxic effects. The tested stilbenoids were evaluated for their ability to attenuate the LPS-stimulated activation of NF-κB/AP-1. Most of the tested substances reduced the activity of NF-κB/AP-1 and later attenuated the expression of TNF-α. The effects of selected stilbenoids were further investigated on inflammatory signaling pathways. Non-prenylated stilbenoids regulated attenuation of NF-ĸB/AP-1 activity upstream by inhibiting the phosphorylation of MAPKs. A docking study used to in silico analyze the tested compounds confirmed their interaction with NF-ĸB, COX-2 and 5-LOX.

• Klíčová slova
• Anti-inflammatory, Cyclooxygenase, Lipoxygenase, Macrophages, Molecular docking simulations, NF-κB, Stilbenes,
• MeSH
• antiflogistika nesteroidní chemie   farmakologie   MeSH
• HCT116 buňky MeSH
• inhibitory cyklooxygenasy 2 chemie   farmakologie   MeSH
• inhibitory lipoxygenas chemie   farmakologie   MeSH
• lidé MeSH
• lipopolysacharidy farmakologie   MeSH
• makrofágy účinky léků   metabolismus   MeSH
• NF-kappa B metabolismus   MeSH
• preklinické hodnocení léčiv metody   MeSH
• prenylace MeSH
• signální transdukce účinky léků   MeSH
• simulace molekulového dockingu MeSH
• stilbeny chemie   farmakologie   MeSH
• TNF-alfa metabolismus   MeSH
• transkripční faktor AP-1 metabolismus   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• 3,3',4,5'-tetrahydroxystilbene MeSH Prohlížeč
• antiflogistika nesteroidní MeSH
• inhibitory cyklooxygenasy 2 MeSH
• inhibitory lipoxygenas MeSH
• lipopolysacharidy MeSH
• NF-kappa B MeSH
• pinostilbene MeSH Prohlížeč
• stilbeny MeSH
• TNF-alfa MeSH
• transkripční faktor AP-1 MeSH

The developmental and epileptic encephalopathies (DEEs) are heterogeneous disorders with a strong genetic contribution, but the underlying genetic etiology remains unknown in a significant proportion of individuals. To explore whether statistical support for genetic etiologies can be generated on the basis of phenotypic features, we analyzed whole-exome sequencing data and phenotypic similarities by using Human Phenotype Ontology (HPO) in 314 individuals with DEEs. We identified a de novo c.508C>T (p.Arg170Trp) variant in AP2M1 in two individuals with a phenotypic similarity that was higher than expected by chance (p = 0.003) and a phenotype related to epilepsy with myoclonic-atonic seizures. We subsequently found the same de novo variant in two individuals with neurodevelopmental disorders and generalized epilepsy in a cohort of 2,310 individuals who underwent diagnostic whole-exome sequencing. AP2M1 encodes the μ-subunit of the adaptor protein complex 2 (AP-2), which is involved in clathrin-mediated endocytosis (CME) and synaptic vesicle recycling. Modeling of protein dynamics indicated that the p.Arg170Trp variant impairs the conformational activation and thermodynamic entropy of the AP-2 complex. Functional complementation of both the μ-subunit carrying the p.Arg170Trp variant in human cells and astrocytes derived from AP-2μ conditional knockout mice revealed a significant impairment of CME of transferrin. In contrast, stability, expression levels, membrane recruitment, and localization were not impaired, suggesting a functional alteration of the AP-2 complex as the underlying disease mechanism. We establish a recurrent pathogenic variant in AP2M1 as a cause of DEEs with distinct phenotypic features, and we implicate dysfunction of the early steps of endocytosis as a disease mechanism in epilepsy.

• Klíčová slova
• Human Phenotype Ontology, clathrin-mediated endocytosis, computational phenotypes, developmental and epileptic encephalopathy, neurodevelopmental disorders, synaptic transmission,
• MeSH
• adaptorový proteinový komplex - mu-podjednotky genetika   MeSH
• adaptorový proteinový komplex 2 genetika   MeSH
• dítě MeSH
• endocytóza * MeSH
• epilepsie etiologie   patologie   MeSH
• klathrin genetika   metabolismus   MeSH
• kojenec MeSH
• lidé MeSH
• missense mutace * MeSH
• mladiství MeSH
• myši knockoutované MeSH
• myši MeSH
• nemoci mozku etiologie   patologie   MeSH
• neurovývojové poruchy etiologie   patologie   MeSH
• předškolní dítě MeSH
• sekvenování exomu MeSH
• zvířata MeSH
• Check Tag
• dítě MeSH
• kojenec MeSH
• lidé MeSH
• mladiství MeSH
• myši MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• adaptor protein complex 2, mu 2 subunit MeSH Prohlížeč
• adaptorový proteinový komplex - mu-podjednotky MeSH
• adaptorový proteinový komplex 2 MeSH
• klathrin MeSH

Selection and internalization of cargo via clathrin-mediated endocytosis requires adaptor protein complexes. One complex, AP-2, acts during cargo selection at the plasma membrane. African trypanosomes lack all components of the AP-2 complex, except for a recently identified orthologue of the AP-2-associated protein kinase 1, AAK1. In characterized eukaryotes, AAK1 phosphorylates the μ2 subunit of the AP-2 complex to enhance cargo recognition and uptake into clathrin-coated vesicles. Here, we show that kinetoplastids encode not one, but two AAK1 orthologues: one (AAK1L2) is absent from salivarian trypanosomes, while the other (AAK1L1) lacks important kinase-specific residues in a range of trypanosomes. These AAK1L1 and AAK1L2 novelties reinforce suggestions of functional divergence in endocytic uptake within salivarian trypanosomes. Despite this, we show that AAK1L1 null mutant Trypanosoma brucei, while viable, display slowed proliferation, morphological abnormalities including swelling of the flagellar pocket, and altered cargo uptake. In summary, our data suggest an unconventional role for a putative pseudokinase during endocytosis and/or vesicular trafficking in T. brucei, independent of AP-2.

• Klíčová slova
• AAK1, AP-2 complex, African trypanosomes, endocytosis,
• MeSH
• buněčná membrána MeSH
• endocytóza fyziologie   MeSH
• klathrin metabolismus   MeSH
• paraziti * metabolismus   MeSH
• Trypanosoma brucei brucei * genetika   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• klathrin MeSH

Bi-allelic loss-of-function variants in genes that encode subunits of the adaptor protein complex 4 (AP-4) lead to prototypical yet poorly understood forms of childhood-onset and complex hereditary spastic paraplegia: SPG47 (AP4B1), SPG50 (AP4M1), SPG51 (AP4E1) and SPG52 (AP4S1). Here, we report a detailed cross-sectional analysis of clinical, imaging and molecular data of 156 patients from 101 families. Enrolled patients were of diverse ethnic backgrounds and covered a wide age range (1.0-49.3 years). While the mean age at symptom onset was 0.8 ± 0.6 years [standard deviation (SD), range 0.2-5.0], the mean age at diagnosis was 10.2 ± 8.5 years (SD, range 0.1-46.3). We define a set of core features: early-onset developmental delay with delayed motor milestones and significant speech delay (50% non-verbal); intellectual disability in the moderate to severe range; mild hypotonia in infancy followed by spastic diplegia (mean age: 8.4 ± 5.1 years, SD) and later tetraplegia (mean age: 16.1 ± 9.8 years, SD); postnatal microcephaly (83%); foot deformities (69%); and epilepsy (66%) that is intractable in a subset. At last follow-up, 36% ambulated with assistance (mean age: 8.9 ± 6.4 years, SD) and 54% were wheelchair-dependent (mean age: 13.4 ± 9.8 years, SD). Episodes of stereotypic laughing, possibly consistent with a pseudobulbar affect, were found in 56% of patients. Key features on neuroimaging include a thin corpus callosum (90%), ventriculomegaly (65%) often with colpocephaly, and periventricular white-matter signal abnormalities (68%). Iron deposition and polymicrogyria were found in a subset of patients. AP4B1-associated SPG47 and AP4M1-associated SPG50 accounted for the majority of cases. About two-thirds of patients were born to consanguineous parents, and 82% carried homozygous variants. Over 70 unique variants were present, the majority of which are frameshift or nonsense mutations. To track disease progression across the age spectrum, we defined the relationship between disease severity as measured by several rating scales and disease duration. We found that the presence of epilepsy, which manifested before the age of 3 years in the majority of patients, was associated with worse motor outcomes. Exploring genotype-phenotype correlations, we found that disease severity and major phenotypes were equally distributed among the four subtypes, establishing that SPG47, SPG50, SPG51 and SPG52 share a common phenotype, an 'AP-4 deficiency syndrome'. By delineating the core clinical, imaging, and molecular features of AP-4-associated hereditary spastic paraplegia across the age spectrum our results will facilitate early diagnosis, enable counselling and anticipatory guidance of affected families and help define endpoints for future interventional trials.

• Klíčová slova
• SPG47, SPG50, SPG51, SPG52, neurodegeneration,
• MeSH
• adaptorový proteinový komplex 4 genetika   MeSH
• corpus callosum diagnostické zobrazování   MeSH
• dítě MeSH
• dospělí MeSH
• kohortové studie MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• magnetická rezonanční tomografie metody   trendy   MeSH
• mladiství MeSH
• mladý dospělý MeSH
• předškolní dítě MeSH
• průřezové studie MeSH
• registrace MeSH
• spastická paraplegie dědičná diagnostické zobrazování   genetika   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• adaptorový proteinový komplex 4 MeSH

The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome.

• MeSH
• adaptorový proteinový komplex 4 genetika   MeSH
• dítě MeSH
• kvadruplegie diagnóza   genetika   MeSH
• lidé MeSH
• mentální retardace diagnóza   genetika   MeSH
• mladiství MeSH
• posunová mutace * MeSH
• sourozenci MeSH
• syndrom MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adaptorový proteinový komplex 4 MeSH

Clathrin-mediated endocytosis (CME) is key to maintaining the transmembrane protein composition of cells' limiting membranes. During mammalian CME, a reversible phosphorylation event occurs on Thr156 of the μ2 subunit of the main endocytic clathrin adaptor, AP2. We show that this phosphorylation event starts during clathrin-coated pit (CCP) initiation and increases throughout CCP lifetime. μ2Thr156 phosphorylation favors a new, cargo-bound conformation of AP2 and simultaneously creates a binding platform for the endocytic NECAP proteins but without significantly altering AP2's cargo affinity in vitro. We describe the structural bases of both. NECAP arrival at CCPs parallels that of clathrin and increases with μ2Thr156 phosphorylation. In turn, NECAP recruits drivers of late stages of CCP formation, including SNX9, via a site distinct from where NECAP binds AP2. Disruption of the different modules of this phosphorylation-based temporal regulatory system results in CCP maturation being delayed and/or stalled, hence impairing global rates of CME.

• Klíčová slova
• AAK1, AP2 endocytic adaptor, NECAP, NMR, Numb-associated kinases (NAK), SNX9, TIRF, clathrin-mediated endocytosis, crystallography, regulation by phosphorylation,
• MeSH
• adaptorový proteinový komplex - alfa-podjednotky genetika   MeSH
• adaptorový proteinový komplex 2 genetika   metabolismus   MeSH
• endocytóza genetika   MeSH
• fosforylace genetika   MeSH
• klathrin genetika   metabolismus   MeSH
• klathrinové vezikuly genetika   metabolismus   MeSH
• lidé MeSH
• potažené jamky v buněčné membráně genetika   metabolismus   MeSH
• třídící nexiny genetika   MeSH
• vazba proteinů genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adaptorový proteinový komplex - alfa-podjednotky MeSH
• adaptorový proteinový komplex 2 MeSH
• klathrin MeSH
• NECAP1 protein, human MeSH Prohlížeč
• SNX9 protein, human MeSH Prohlížeč
• třídící nexiny MeSH

Here we report the comprehensive characterization of the secondary metabolites from the leaves of Colebrookea oppositifolia Smith, a species used as medicinal plant in the traditional medicine of Nepal. Phytochemical screening of bioactives was performed using an integrated LC-MSn and high resolution MS (Mass Spectrometry) approach. Forty-three compounds were tentatively identified, mainly aglyconic and glycosilated flavonoids and phenolic acids, as well as other bioactives such as coumarins and terpenes were detected. Furthermore, the NF-κB and AP-1 inhibitory activity of C. oppositifolia extract were evaluated, as well as its cytotoxicity against THP-1 cells, in order to assess the potential use of this herb as a source of anti-inflammatory and cytotoxic compounds. The results so far obtained indicate that C. oppositifolia leaves extract could significantly reduce the viability of THP-1 cells (IC50 = 6.2 ± 1.2 µg/mL), as well as the activation of both NF-κB and AP-1 at the concentration of 2 μg/mL. Our results indicate that Nepalese C. oppositifolia is a valuable source of anti-inflammatory and cytotoxic compounds. The phytochemical composition reported here can partially justify the traditional uses of C. oppositifolia in Nepal, especially in the treatment of inflammatory diseases, although further research will be needed to assess the full potential of this species.

• Klíčová slova
• Colebrookea oppositifolia, anti-AP-1, anti-NF-κB, cytotoxic activity, secondary metabolites,
• MeSH
• antiflogistika izolace a purifikace   farmakologie   toxicita   MeSH
• chromatografie kapalinová MeSH
• flavonoidy analýza   izolace a purifikace   MeSH
• hluchavkovité metabolismus   MeSH
• hmotnostní spektrometrie MeSH
• hydroxybenzoáty analýza   izolace a purifikace   MeSH
• léčivé rostliny metabolismus   MeSH
• lidé MeSH
• listy rostlin metabolismus   MeSH
• metabolom MeSH
• methanol MeSH
• NF-kappa B antagonisté a inhibitory   MeSH
• rostlinné extrakty chemie   izolace a purifikace   farmakologie   toxicita   MeSH
• THP-1 buňky MeSH
• transkripční faktor AP-1 antagonisté a inhibitory   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Nepál MeSH
• Názvy látek
• antiflogistika MeSH
• flavonoidy MeSH
• hydroxybenzoáty MeSH
• methanol MeSH
• NF-kappa B MeSH
• phenolic acid MeSH Prohlížeč
• rostlinné extrakty MeSH
• transkripční faktor AP-1 MeSH

Herpes simplex virus (HSV) causes numerous mild-to-serious human diseases, including mucocutaneous herpes infections and life-threatening herpes encephalitis. Moreover, herpes viral lesions can be complicated by inflammation and secondary bacterial infections. The development of resistance to antiviral drugs along with the undesirable side effects of these drugs are relevant argue for the development of new anti-HSV drugs with diverse mechanisms of action. Eucalyptus extracts have been used for decades to combat various infectious diseases. We isolated and studied 12 pure compounds and one mixture of two constitutional isomers from the leaves and twigs of E. globulus. The structures were identified by spectroscopic methods (NMR, HR-MS, IR) and all of them were tested for antiherpetic activity against the replication of antigen types HSV-1 and HSV-2. Tereticornate A (12) (IC50: 0.96 μg/mL; selectivity index CC50/IC50: 218.8) showed the strongest activity in the anti-HSV-1 assay, even greater than acyclovir (IC50: 1.92 μg/mL; selectivity index CC50/IC50: 109.4), a standard antiviral drug. Cypellocarpin C (5) (EC50: 0.73 μg/mL; selectivity index CC50/EC50: 287.7) showed the most potent anti-HSV-2 activity, also more intensive than acyclovir (EC50: 1.75 μg/mL; selectivity index CC50/EC50: 120.0). The antimicrobial activity of the isolated compounds was also evaluated against the bacteria Staphylococcus aureus, Bacillus cereus, Escherichia coli, and Pseudomonas aeruginosa and the yeast Candida albicans. The anti-inflammatory potential was examined using LPS-stimulated THP-1-XBlue™-MD2-CD14 and THP-1 macrophages and focusing on the influences of the NF-κB/AP-1 activity and the secretion of pro-inflammatory cytokines IL-1β and TNF-α.

• Klíčová slova
• Eucalyptus, HSV-1, HSV-2, IL-1β, NF-κB/AP-1, ROS, TNF-α, anti-inflammatory, antibacterial, antiherpetic,
• MeSH
• antibakteriální látky chemie   farmakologie   MeSH
• antiflogistika chemie   farmakologie   MeSH
• antiinfekční látky chemie   farmakologie   MeSH
• antioxidancia metabolismus   MeSH
• antivirové látky chemie   farmakologie   MeSH
• buněčné linie MeSH
• Cercopithecus aethiops MeSH
• cytokiny metabolismus   MeSH
• Eucalyptus chemie   MeSH
• herpes simplex metabolismus   virologie   MeSH
• lidé MeSH
• NF-kappa B metabolismus   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• rostlinné extrakty chemie   farmakologie   MeSH
• Simplexvirus účinky léků   fyziologie   MeSH
• transkripční faktor AP-1 metabolismus   MeSH
• Vero buňky MeSH
• viabilita buněk účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• antibakteriální látky MeSH
• antiflogistika MeSH
• antiinfekční látky MeSH
• antioxidancia MeSH
• antivirové látky MeSH
• cytokiny MeSH
• NF-kappa B MeSH
• reaktivní formy kyslíku MeSH
• rostlinné extrakty MeSH
• transkripční faktor AP-1 MeSH

Endocytosis is an essential eukaryotic process that maintains the homeostasis of the plasma membrane proteome by vesicle-mediated internalization. Its predominant mode of operation utilizes the polymerization of the scaffold protein clathrin forming a coat around the vesicle; therefore, it is termed clathrin-mediated endocytosis (CME). Throughout evolution, the machinery that mediates CME is marked by losses, multiplications, and innovations. CME employs a limited number of conserved structural domains and folds, whose assembly and connections are species dependent. In plants, many of the domains are grouped into an ancient multimeric complex, the TPLATE complex, which occupies a central position as an interaction hub for the endocytic machinery. In this review, we provide an overview of the current knowledge regarding the structural aspects of plant CME, and we draw comparisons to other model systems. To do so, we have taken advantage of recent developments with respect to artificial intelligence-based protein structure prediction.

• Klíčová slova
• AP-2 complex, TPLATE complex, clathrin-mediated endocytosis, evolutionarily conserved folds, modular domain architecture,
• MeSH
• biologická evoluce MeSH
• buněčná membrána metabolismus   MeSH
• endocytóza * fyziologie   MeSH
• klathrin * metabolismus   chemie   MeSH
• molekulární evoluce MeSH
• rostlinné proteiny metabolismus   chemie   genetika   MeSH
• rostliny * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• klathrin * MeSH
• rostlinné proteiny MeSH