The regulation of junctional actin dynamics by cell adhesion receptors

Steinbacher, Tim; Ebnet, Klaus

doi:10.1007/s00418-018-1691-8

Cited by 19 publications

(17 citation statements)

References 77 publications

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“…Interestingly, NC1‐peptide overexpression in the testis also downregulated PCP protein Dvl3, but not Fzd3 and Prickle 1 (Figure A,B). Furthermore, NC1‐peptide overexpression downregulated actin nucleation proteins Spire 1 and formin 1, actin barbed end capping and bundling protein Eps8, but a mild and persistent upregulation of Arp3 was noted (Figure A,B), wherein Arp3 together with Arp2 create the Arp2/3 complex which is known to induce branched actin polymerization, converting bundled actin filaments into a branched network, thereby destabilizing the F‐actin network …”

Section: Resultsmentioning

confidence: 99%

NC1‐peptide regulates spermatogenesis through changes in cytoskeletal organization mediated by EB1

Liu

et al. 2020

FASEB j.

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are contributed equally to the completion of this work.Abbreviations: +TIP, microtubule plus (+)-end tracking protein; AJ, adherens junction; aPKC, atypical protein kinase C; Arp3, actin-related protein 3; BM, basement membrane; BTB, blood-testis barrier; Crb3, Crumbs homolog-3; DAPI, 4', 6-diamidino-2-phenylindole; Dia1, Diaphanous-related formin-1; Dlg1, Discs large 1; Dvl3, Disheveled 3; EB1, end-binding protein 1; Eps8, epidermal growth factor receptor pathway substrate 8; ES, ectoplasmic specialization; Fzd3, Frizzled 3; F12/DMEM, Ham's F12 nutrient mixture/Dulbecco's modified Eagle's medium (1:1, vol/vol); GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GJ, gap junction; H&E, hematoxylin and eosin staining; IF, immunofluorescence microscopy; IgG, immunoglobulin; IP, immunoprecipitation; MAP1a, microtubule-associated protein 1a; MARK, microtubule affinity-regulatory kinase 4; MT, microtubule; mTOR, mammalian target of rapamycin; NC1 domain, non-collagenous domain 1; Pals1, protein associated with Lin-7 1; PatJ, Pals1-associated tight junction protein; Par6, partitioning-defective (Par) protein 6; rpS6, ribosomal protein S6; TJ, tight junction; ZO-1, zonula occludens-1. AbstractDuring the epithelial cycle of spermatogenesis, different sets of cellular events take place across the seminiferous epithelium in the testis. For instance, remodeling of the blood-testis barrier (BTB) that facilitates the transport of preleptotene spermatocytes across the immunological barrier and the release of sperms at spermiation take place at the opposite ends of the epithelium simultaneously at stage VIII of the epithelial cycle. These cellular events are tightly coordinated via locally produced regulatory biomolecules. Studies have shown that collagen α3 (IV) chains, a major constituent component of the basement membrane, release the non-collagenous (NC) 1 domain, a 28-kDa peptide, designated NC1-peptide, from the C-terminal region, via the action of MMP-9 (matrix metalloproteinase 9). NC1-peptide was found to be capable of inducing BTB remodeling and spermatid release across the epithelium. As such, the NC1-peptide is an endogenously produced biologically active peptide which coordinates these cellular events across the epithelium in stage VIII tubules. Herein, we used an animal model, wherein NC1-peptide cloned into the pCI-neo mammalian expression vector was overexpressed in the testis, to better understanding the molecular mechanism by which NC1-peptide regulated spermatogenic function. It was shown that NC1-peptide induced considerable downregulation on a number of cell polarity and planar cell polarity (PCP) proteins, and studies have shown these polarity and PCP proteins modulate spermatid polarity and adhesion via their effects on microtubule (MT) and F-actin cytoskeletal organization across the epithelium. More important, NC1-peptide exerted its effects by downregulating the expression of microtubule (MT) plus-end tracking protein (+TIP) called EB1 (end-binding protein 1). We cloned the full-length EB1 cDNA for its ov...

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Section: Resultsmentioning

confidence: 99%

NC1‐peptide regulates spermatogenesis through changes in cytoskeletal organization mediated by EB1

Liu

et al. 2020

FASEB j.

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“…Basal to the tight junctions are the adherens junctions, which mediate cell-cell adhesion and signaling (Harris and Tepass, 2010b), and contain E-cadherin (Ecad hereafter) and nectin family proteins. Interaction between Ecad molecules in trans promotes intercellular adhesion and coupling to the actomyosin cytoskeleton through the catenin adapter proteins α-catenin and β-catenin (Lecuit and Yap, 2015;Steinbacher and Ebnet, 2018). In addition, some tissues have desmosomes, which contain cadherin-like proteins that are linked to keratin intermediate filaments to form spot-like junctions at the lateral membrane.…”

Section: Epithelial Cell Polaritymentioning

confidence: 99%

Regulation of Cdc42 and its effectors in epithelial morphogenesis

Pichaud

Walther

Almeida

2019

Journal of Cell Science

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Cdc42a member of the small Rho GTPase familyregulates cell polarity across organisms from yeast to humans. It is an essential regulator of polarized morphogenesis in epithelial cells, through coordination of apical membrane morphogenesis, lumen formation and junction maturation. In parallel, work in yeast and Caenorhabditis elegans has provided important clues as to how this molecular switch can generate and regulate polarity through localized activation or inhibition, and cytoskeleton regulation. Recent studies have revealed how important and complex these regulations can be during epithelial morphogenesis. This complexity is mirrored by the fact that Cdc42 can exert its function through many effector proteins. In epithelial cells, these include atypical PKC (aPKC, also known as PKC-3), the P21activated kinase (PAK) family, myotonic dystrophy-related Cdc42 binding kinase beta (MRCKβ, also known as CDC42BPB) and neural Wiskott-Aldrich syndrome protein (N-WASp, also known as WASL).Here, we review how the spatial regulation of Cdc42 promotes polarity and polarized morphogenesis of the plasma membrane, with a focus on the epithelial cell type.

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“…For example, a prominent invasively transition of cancer cells occurs independent of mechanics of ECM, while cell migration, proliferation, and differentiation of normal cells rely on ECM adhesivity . Increasing ECM elasticity induces malignant phenotypes independent of ligand density by activation of the focal adhesion (FA) signaling pathway, while normal cells are more sensitive to adhesive factors mediating through adherens junction (AJ) signaling pathway …”

Section: Introductionmentioning

confidence: 99%

Impact of Hydrogel Elasticity and Adherence on Osteosarcoma Cells and Osteoblasts

Jiang

Chen

et al. 2019

Adv Healthcare Materials

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Biochemical and physical properties of extracellular matrix (ECM) control cell behaviors, but how they affect osteosarcoma cells that do not require attachment and their normal counterparts (osteoblasts) that are anchorage‐dependent has not been reported yet. In this study, the effects of matrix elasticity and adherence on osteosarcoma MG63 cells are investigated using four types of scaffolds (collagen type I, matrigel, alginate, and agarose) with varied adhesion ligands and rigidity, as compared with osteoblast hFOB1.19 cells. MG63 cells on 2D films are sensitive to ECM adherence, similar to the situation of hFOB1.19 cultured in both 2D and 3D. However, osteosarcoma cells in 3D hydrogels are sensitive to ECM elasticity rather than adherence, with tumor proliferation and malignancy varied with matrix rigidity. The results indicate that osteosarcomas cells might adopt unnatural characteristics on flat surfaces. But in 3D culture, they recover their normal state independent of adherence, as regulated mainly by ECM elasticity via the integrin‐mediated focal adhesion pathway, which is further confirmed by in vivo studies. In contrast, osteoblasts and 2D cultured osteosarcoma cells are predominantly influenced by ECM bioactivity regulated by integrin‐mediated adherens junction pathway. This study might provide new insights into rational design of scaffolds for tumor/tissue engineering.

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The regulation of junctional actin dynamics by cell adhesion receptors

Cited by 19 publications

References 77 publications

NC1‐peptide regulates spermatogenesis through changes in cytoskeletal organization mediated by EB1

NC1‐peptide regulates spermatogenesis through changes in cytoskeletal organization mediated by EB1

Regulation of Cdc42 and its effectors in epithelial morphogenesis

Impact of Hydrogel Elasticity and Adherence on Osteosarcoma Cells and Osteoblasts

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