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Cytoskeletons (F-actin) and spermatogenesis
Published in C. Yan Cheng, Spermatogenesis, 2018
Liza O’Donnell, Peter G. Stanton
Various actin-binding proteins are found at the basal ES, with functions including actin bundling and cross-linking (espin, ezrin, fascin 1, palladin, plastin family), branched actin polymerization (Arp2/3 complex, N-WASP), end-capping (Eps8), and branch stabilization (cortactin).68,69 Selective RNAi-mediated knockdown of individual actin-binding protein expression tends to disturb Sertoli cell junction function in vitro as well as F-actin and associated junction protein organization (e.g., targeting fascin 170). However, under these circumstances ES function is not completely ablated, suggesting that multiple proteins contribute to actin dynamics at the basal ES. In contrast, targeted disruption of the branched actin polymerization pathway by knockout of N-Wasp (which acts upstream of Arp2/3) in mouse Sertoli cells caused spermatogenic arrest, loss of expression of connexin-43 and occludin (markers for gap and tight junctions, respectively), and loss of BTB function.71 These studies clearly show control of branched actin polymerization to be an essential component of the maintenance of seminiferous epithelial structure and function.
Epithelial and fibroepithelial tumors
Published in Eckart Haneke, Histopathology of the NailOnychopathology, 2017
Immunohistochemistry has often claimed to be of discriminative value; however, the differences are usually only quantitative. There is no difference in p16 expression.145 Compared to SCC, keratoacanthoma demonstrates a more regular peripheral p53, PCNA, and MiB1 (Ki67) staining than SCC. The same is true for the nuclear factor kappa B p50 subunit and cortactin that shows a peripheral pattern in keratoacanthoma and a more scattered pattern in SCC.146 Also, p63 does not reliably distinguish KA from SCC.147 Whereas tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is negative in keratoacanthoma, it is from strong to absent in SCC.148 SCC expresses more caspase149 and apoptosis inducing factor than KA.150 However, SCC also expresses more Bcl-x, which is a member of the Bcl-2 antiapoptosis protein family.151,152 Ezrin, a cytoskeleton linker protein actively involved in regulating the growth and metastatic capacity of cancer cells, is markedly expressed in the cytoplasm of SCC, whereas KA shows only cellular membrane expression.153
Neisseria meningitidis
Published in Peter M. Lydyard, Michael F. Cole, John Holton, William L. Irving, Nino Porakishvili, Pradhib Venkatesan, Katherine N. Ward, Case Studies in Infectious Disease, 2010
Peter M. Lydyard, Michael F. Cole, John Holton, William L. Irving, Nino Porakishvili, Pradhib Venkatesan, Katherine N. Ward
The nasopharyngeal epithelium is induced to take up the meningococci by receptor-mediated endocytosis and the bacteria pass through the cells into the subepithelial space where infection is established. From this site the meningococci may seed the bloodstream where production of capsule is important for survival and from there to the meninges and many other sites including joints and the skin. Type IV pili mediate adhesion of N. meningitidis to endothelial cells and induce Rho- and Cdc42-dependent cortical actin polymerization that results in the formation of membrane protrusions that lead to bacterial uptake. An essential step in the formation of membrane protrusions appears to be the phosphorylation of cortactin because it controls the polymerization of cortical actin. LOS plays an essential role in the induction of membrane protrusions because it induces the recruitment and phosphorylation of cortactin.
Dual role of E-cadherin in cancer cells
Published in Tissue Barriers, 2022
Svetlana N. Rubtsova, Irina Y. Zhitnyak, Natalya A. Gloushankova
Actin filaments nucleate at AJs,27 but the mechanisms of actin filament polymerization at AJs are not well understood. It has been suggested that the Arp2/3 complex is involved in the nucleation of junctional actin filaments as it was shown that establishment of E-cadherin-based adhesion promotes recruitment of Arp2/3 to the AJs.28 Activators of the Arp2/3 complex, such as WAVE and N-WASP, have also been detected at epithelial AJs.22,29 Cortactin, which directly binds WAVE2 and Arp2/3 at ZA, may also regulate the junctional actin cytoskeleton.30 Formins promoting elongation of linear actin filaments may be involved in the assembly of actin filaments at AJs. It was demonstrated that RhoA effector Dia1 was essential for the formation and maintenance of linear AJs in MCF-7 cells.31 In MCF10A cells grown in Matrigel, the junctional actin assembly was mediated by Formin-like 2 downstream of Rac1.32
S1P in the development of atherosclerosis: roles of hemodynamic wall shear stress and endothelial permeability
Published in Tissue Barriers, 2021
Christina M Warboys, Peter D Weinberg
The formation of prominent cortical actin bands in response to S1P was also associated with rapid translocation of the actin-binding protein, cortactin, which promotes cytoskeletal remodeling by stimulating and stabilizing Arp2/3-mediated actin polymerization at filament branch points; this was found to be important in mediating the barrier-enhancing effects of S1P.36 The localization of cortactin to cortical actin bands following exposure to S1P was dependent on Rac activation but occurred independently of PAK activity, although it is possible that interaction of cortactin with PAK is required.36 The localization of cortactin to the peripheral actin bands was found to promote MLC phosphorylation via its interaction with non-muscle myosin light-chain kinase-2 (nmMLCK2).36 Atomic force microscopy revealed that S1P rapidly increases the elastic modulus (stiffening) at the cell periphery in a cortactin-dependent manner, suggesting that localized cytoskeletal actomyosin tension within cortical bands may mechanically strengthen cell–cell junctions to increase barrier function.63,64
Role of vacuolating cytotoxin A in Helicobacter pylori infection and its impact on gastric pathogenesis
Published in Expert Review of Anti-infective Therapy, 2020
Shamshul Ansari, Yoshio Yamaoka
The alteration of several cellular proteins has been linked with the development and progression of cancer. Cortactin (cortical actin-binding protein), a filamentous actin-binding protein, is an activator of actin-related protein complexes (ARP)2/3 and important molecular link between signal transduction pathways and the cytoskeleton [109110111112114–113]. In cancer tissue samples, the expression of the cortactin gene is abnormally high and is associated with cancer cell metastasis [114115116–117]. In an in-vitro study, AGS gastric epithelial cells that expressed cortactin and were treated with VacA showed a significant increase in the percentage of apoptotic cells and expression of the proapoptotic protein Bax, whereas a decrease in the expression of the antiapoptotic protein Bcl-2 was observed, suggesting the role of VacA in association with cortactin for gastric pathogenicity [118]. Similarly, the role of connexin 43 (Cx43), a member of the human Cx family, is responsible for VacA-induced cell death and gastric pathogenicity [119,120]. The Cx-family proteins are membrane proteins that form channels at gap junctions to regulate development and homeostasis via intercellular communication, cell-cell channel formation, and exchange of signaling molecules [121122–123]. A recent in-vitro study demonstrated the role of Cx43 in VacA-induced AZ-521 cell death via a Rac1/ERK-dependent pathway in H. pylori-infected gastric mucosa [124]. Elevated Cx43 level in H. pylori-infected gastric tissue is observed, which is associated with erosive gastritis.