Neisseria meningitidis
Peter M. Lydyard, Michael F. Cole, John Holton, William L. Irving, Nino Porakishvili, Pradhib Venkatesan, Katherine N. Ward in Case Studies in Infectious Disease, 2010
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.
Epithelial and fibroepithelial tumors
Eckart Haneke in 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
Cytoskeletons (F-actin) and spermatogenesis
C. Yan Cheng in Spermatogenesis, 2018
TBCs are also involved in junction removal between Sertoli cells and spermatids during spermiation. Spermiation is the process by which mature spermatids undergo a final remodeling, including removal of their extensive cytoplasm and remodeling of the nucleus, prior to their disengagement or release from the Sertoli cell.72 In order for spermiation to occur, the extensive ES junction present around the spermatid (Figure 15.2) needs to be removed. The removal of ES likely involves the disassembly of the extensive actin bundles by proteins involved in F-actin dynamics (e.g., formin 190). In addition, TBCs likely remove ES structures. TBCs form and internalize both Sertoli cell and spermatid plasma membranes together with the junction-associated proteins.69,91 The bulbar portion of the TBC then buds off and becomes internalized into the Sertoli cell as an endocytic vesicle; in this way TBCs are able to remove ES and associated adhesion junctions between the Sertoli cell and the spermatid in preparation for its final disengagement.69,91 There are now many lines of evidence to show that F-actin dynamics control TBC formation and their ability to remove ES and other junction-associated proteins to ready the spermatid for disengagement. For example, disruption of F-actin with cytochalasin D prevents TBC formation and normal spermiation.92 The F-actin “cuffs” around the tubular portion of TBCs contains various proteins involved in actin branching, including the Arp2/3 complex, N-WASP and paxillin.69 Estradiol treatment reduces F-actin-associated proteins within TBCs, causing defective TBC formation and spermiation failure.78 Importantly, knockdown of cortactin, the protein that stabilizes actin branches, prevents normal TBC formation and impairs spermiation.93
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.
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
Acute application of shear stress (up to 20 mins) induces rapid cytoskeletal remodeling in a similar manner to that observed following acute exposure to S1P. Alongside a rapid increase in transendothelial electrical resistance, acute application of atheroprotective shear stress to human pulmonary artery EC results in dynamic cytoskeletal remodeling to form prominent cortical actin bands52,73 and rapid activation and translocation of Rac to the cell periphery.52 This is associated with increased MLC phosphorylation, tyrosine phosphorylation of junctional proteins and increased localization of cortactin to the periphery.73 Atheroprotective shear stress also results in the localization of paxillin, FAK, GIT1 and GIT2 to the cell periphery along with increased phosphorylation of FAK on tyrosine576, consistent with formation of new focal adhesions at the cell periphery.52 The effects of shear stress on cytoskeletal remodeling and junctional proteins are summarized in Figure 4.
High Expression of TRIM15 Is Associated with Tumor Invasion and Predicts Poor Prognosis in Patients with Gastric Cancer
Published in Journal of Investigative Surgery, 2021
Weiran Zhou, Hao Chen, Yuanyuan Ruan, Xiaoqing Zeng, Fenglin Liu
There are two studies carried out on TRIM15 both focusing on its role in focal adhesion. One research identified TRIM15 as a curial component of focal adhesions. It localized to focal adhesions by binding to paxillin through its coiled-coil domain. TRIM15-depleted HeLa cells displayed impaired cell migration [23]. This matches well with our data showing enhanced migration and metastasis when TRIM15 expression is enhanced. However, the other study came to the conclusion that TRIM15 could inhibit colon cancer development and was a negative regulator of cell motility in colon epithelial cells. TRIM15 interacted with several adaptors or scaffold proteins for actin cytoskeleton dynamics. Cortactin (CTTN) is one of these proteins playing a critical role in cell motility. In TRIM15-overexpressed cells, the phosphorylation of CTTN which allowed cell movement was inhabited. It suggested that TRIM15 may inhibit cell migration by impairing phosphorylation of CTTN[18]. The contradictory results could be partially due to the different cell lines since one study used HeLa cells while the other used colon epithelial cells. Notably, CTTN is known to a negative or positive regulator of cell migration depends on different types of cancer. In colon cancer the phosphorylation of CTTN increases cell migration whereas in gastric cancer hyperphosphorylated CTTN plays an inhibitory role in cell motility [29]. What’s more, it has been reported that overexpression of paxillin correlates with tumor progression and poor survival in patients with gastric cancer [30], suggesting that the role of TRIM15 in gastric cancer might be facilitated by its interaction with paxillin. Certainly, the precise biological function of TRIM15 still needs further investigation.
Related Knowledge Centers
- Actin
- Cell Migration
- Cytoplasm
- Cytoskeleton
- Invadopodia
- Lamellipodium
- Protein
- Arp2/3 Complex
- Endocytosis
- Gene