Epithelia are multicellular sheets that form barriers defining the internal and external environments. The constant stresses acting at this interface require that epithelial sheets are mechanically robust and provide a selective barrier to the hostile exterior. These properties are mediated by cellular junctions which are physically linked with heavily crosslinked cytoskeletal networks. Such hardwiring is facilitated by plakins, a family of giant modular proteins which serve as 'molecular bridges' between different cytoskeletal filaments and multiprotein adhesion complexes. Dysfunction of cytoskeletal crosslinking compromises epithelial biomechanics and structural integrity. Subsequent loss of barrier function leads to disturbed tissue homeostasis and pathological consequences such as skin blistering or intestinal inflammation. In this article, we highlight the importance of the cytolinker protein plectin for the functional organization of epithelial cytoskeletal networks. In particular, we focus on the ability of plectin to act as an integrator of the epithelial cytoarchitecture that defines the biomechanics of the whole tissue. Finally, we also discuss the role of cytoskeletal crosslinking in emerging aspects of epithelial mechanobiology that are critical for the maintenance of epithelial homeostasis.

• Klíčová slova
• cytoskeletal crosstalk, epithelia, mechanobiology, plectin,
• MeSH
• biomechanika MeSH
• cytoskelet * metabolismus   MeSH
• epitelové buňky metabolismus   cytologie   MeSH
• lidé MeSH
• plektin * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• plektin * MeSH

The coordinated interplay of cytoskeletal networks critically determines tissue biomechanics and structural integrity. Here, we show that plectin, a major intermediate filament-based cytolinker protein, orchestrates cortical cytoskeletal networks in epithelial sheets to support intercellular junctions. By combining CRISPR/Cas9-based gene editing and pharmacological inhibition, we demonstrate that in an F-actin-dependent context, plectin is essential for the formation of the circumferential keratin rim, organization of radial keratin spokes, and desmosomal patterning. In the absence of plectin-mediated cytoskeletal cross-linking, the aberrant keratin-desmosome (DSM)-network feeds back to the actin cytoskeleton, which results in elevated actomyosin contractility. Also, by complementing a predictive mechanical model with Förster resonance energy transfer-based tension sensors, we provide evidence that in the absence of cytoskeletal cross-linking, major intercellular junctions (adherens junctions and DSMs) are under intrinsically generated tensile stress. Defective cytoarchitecture and tensional disequilibrium result in reduced intercellular cohesion, associated with general destabilization of plectin-deficient sheets upon mechanical stress.

• MeSH
• aktiny metabolismus   MeSH
• biomechanika MeSH
• buňky MDCK MeSH
• cytoskelet metabolismus   ultrastruktura   MeSH
• desmozomy metabolismus   ultrastruktura   MeSH
• epitelové buňky metabolismus   ultrastruktura   MeSH
• genový knockout MeSH
• keratiny metabolismus   MeSH
• lidé MeSH
• MFC-7 buňky MeSH
• myši MeSH
• pevnost v tahu MeSH
• plektin metabolismus   MeSH
• protein - isoformy metabolismus   MeSH
• psi MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• aktiny MeSH
• keratiny MeSH
• plektin MeSH
• protein - isoformy MeSH

Plectin, a highly versatile cytolinker protein, provides tissues with mechanical stability through the integration of intermediate filaments (IFs) with cell junctions. Here, we hypothesize that plectin-controlled cytoarchitecture is a critical determinant of the intestinal barrier function and homeostasis. Mice lacking plectin in an intestinal epithelial cell (IEC; PleΔIEC) spontaneously developed colitis characterized by extensive detachment of IECs from the basement membrane (BM), increased intestinal permeability, and inflammatory lesions. Moreover, plectin expression was reduced in the colons of ulcerative colitis (UC) patients and negatively correlated with the severity of colitis. Mechanistically, plectin deficiency in IECs led to aberrant keratin filament (KF) network organization and the formation of dysfunctional hemidesmosomes (HDs) and intercellular junctions. In addition, the hemidesmosomal α6β4 integrin (Itg) receptor showed attenuated association with KFs, and protein profiling revealed prominent downregulation of junctional constituents. Consistent with the effects of plectin loss in the intestinal epithelium, plectin-deficient IECs exhibited remarkably reduced mechanical stability and limited adhesion capacity in vitro. Feeding mice with a low-residue liquid diet that reduced mechanical stress and antibiotic treatment successfully mitigated epithelial damage in the PleΔIEC colon.

• MeSH
• desmozomy genetika   metabolismus   MeSH
• dospělí MeSH
• keratiny metabolismus   MeSH
• kolitida metabolismus   prevence a kontrola   MeSH
• kolon patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• modely nemocí na zvířatech MeSH
• myši knockoutované MeSH
• myši MeSH
• plektin genetika   metabolismus   MeSH
• senioři MeSH
• střevní sliznice metabolismus   patologie   MeSH
• ulcerózní kolitida metabolismus   prevence a kontrola   MeSH
• zvířata MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• myši MeSH
• senioři MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• keratiny MeSH
• plektin MeSH

Using both monoclonal and polyclonal antibodies against mammalian plectin (multifunctional protein cross-linking cytoskeletal structures, mainly intermediate filaments, in mammalian cells), several putative isoforms of plectin-like proteins were found in protein extracts from the green alga Chlamydomonas eugametos (Volvocales). Immunofluorescence and immunoblotting revealed that some of the plectin-like proteins were present in perinuclear region or localized near the cell wall, probably being attached to the cytoplasmic membrane.

• MeSH
• bílkoviny řas metabolismus   MeSH
• Chlamydomonas metabolismus   MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• fluorescenční protilátková technika MeSH
• imunoblotting MeSH
• králíci MeSH
• plektin MeSH
• proteiny intermediálních filament metabolismus   MeSH
• subcelulární frakce metabolismus   MeSH
• zvířata MeSH
• Check Tag
• králíci MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bílkoviny řas MeSH
• plektin MeSH
• proteiny intermediálních filament MeSH