Cytoskeletons (F-actin) and spermatogenesis
C. Yan Cheng in Spermatogenesis, 2018
Actin monomers are relatively flat proteins with a cleft that binds tightly to ATP, which is hydrolyzed during polymerization. Monomers spontaneously dimerize then polymerize into a helical single-stranded filament (Figure 15.1a). Due to the orientation of actin monomers at each end, F-actin has a “pointy end,” which is slow to polymerize, and a “barbed end,” which rapidly polymerizes and grows in length (Figure 15.1). Profilin is a small protein that plays a major role in actin polymerization via binding to monomers (Figure 15.1a) and to the polymerized filament and cytoskeletal proteins.4 Once polymerized, actin filaments can be cross-linked into higher-order structures via association with various microtubule-associated proteins (Figure 15.1b), (reviewed in Pollard 2016).1 The complexity of actin structures is further increased by branching, facilitated by the Arp2/3 complex. The Arp2/3 complex, in association with nucleation promoting factors such as WASH and WASP, binds to the side of a filament and nucleates a daughter branch,5 whereas cortactin stabilizes the branches (Figure 15.1b).
Gateways of Pathogenic Bacterial Entry into Host Cells—Salmonella
K. Balamurugan, U. Prithika in Pocket Guide to Bacterial Infections, 2019
Besides all these well-documented entry mechanisms, some other unidentified and unfamiliar factors seems to be involved during cell invasion. Rosselin et al. (2011) demonstrated that Salmonella serovars that were not expressing the effectors like Rck, PagN, and T3SS-1 have the ability to invade different host cells by unknown mechanism. This unknown entry mechanism depends on the cell type and cell line. For example, 3T3 fibroblasts and MA104 kidney epithelial cells are most accommodating to these mechanisms to enter independently of T3SS-1, PagN, and Rck. But nonpolarized HT29 enterocytes are not prone to these unknown entry mechanisms. They stated that cytoskeletal and membrane rearrangements similar to zipper or trigger machinery system have been observed during microscopic examination of infected cell types. These factors are found to be involved in inducing the signaling cascade that mediate the Salmonella entry into human foreskin fibroblasts (Aiastui et al. 2010). Steffen et al. (2004) and Hanisch et al. (2012) described a new invasion pathway that could be independent of Arp2/3 complex, and it depends on the formation of myosin II-rich stress fiber-like structures at entry sites via the activation of RhoA/Rho kinase signaling pathway.
Mucosal interactions with enteropathogenic bacteria
Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald in Principles of Mucosal Immunology, 2020
Extracellular pathogens such as EPEC and EHEC induce the formation of actin-rich pedestal structures on the host epithelial surface where they can reside and grow. Via T3SS, they deliver the effector protein Tir, which embeds itself into the host membrane and binds the bacterial outer membrane protein intimin. Tir intracellular domain, either directly (EPEC) or indirectly via another bacterial effector (EHEC), stimulates an intracellular cascade that activates the host protein N-WASP (neural Wiskott–Aldrich syndrome protein). In turn, N-WASP recruits the seven-protein Arp2/3 complex that mediates actin polymerization and formation of the pedestal beneath the extracellular bacterium (see Figure 25.3).
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
Uncovering the proteome response of murine neuroblastoma cells against low-dose exposure to saxitoxin
Published in Toxicology Mechanisms and Methods, 2018
Xiao Chen, Ye Sun, Haiyan Huang, Wei Liu, Panpan Hu, Xinfeng Huang, Fei Zou, Jianjun Liu
Low-dose saxitoxin exposure (10 nM for 24 h) elevated the expressions of ENO1 and CFL2, whereas it decreased the expressions of ARP5L. These three proteins were claimed essential in cell skeleton in previous studies. ARP5L is a subunit of ARP2/3 complex which modulates actin polymerization (Mullins et al. 1998). The interaction between ENO1 and microtubules affects the dynamism of the cytoskeletal filaments during the transition from myoblast to myotubes (Keller et al. 2007). The expression of ENO1 reduces during the early stages of human myogenesis (Fougerousse et al. 2001). CFL2, a small actin-binding protein, promotes the actin filament assembly and maintains the stability of the actin filament (Vartiainen et al. 2002). The expression of CFL2 is crucial for early stage development of muscle (Agrawal et al. 2012). The perturbations of these protein suggested that low-dose exposure of saxitoxin affected the stability of cell skeleton. These findings associated with the paralysis and the numbness after the saxitoxin exposure and also correlated to the developmental toxicity of the low-dose saxitoxin exposure.
Dual role of ARPC1B in regulating the network between tumor-associated macrophages and tumor cells in glioblastoma
Published in OncoImmunology, 2022
Tianqi Liu, Chen Zhu, Xin Chen, Jianqi Wu, Gefei Guan, Cunyi Zou, Shuai Shen, Ling Chen, Peng Cheng, Wen Cheng, Anhua Wu
Accordingly, the aim of this study was to identify key genes associated with TAMs in GBM that are linked to tumor progression, as well as to explore the underlying mechanism. In this study, we reveal ARPC1B (actin-related protein 2/3 complex subunit 1B) as a novel regulator for GBM-TAM regulation. Actin-related protein 2/3 complex (Arp2/3) is an evolutionary conserved molecular machine that generates branched actin networks.8 Over the years, dysregulation of the Arp2/3 regulatory system in cancer has been described that excessive activation of the Arp2/3 complex commonly promotes tumor progression.9–11 ARPC1B is one of the regulatory subunits of Arp2/3 complex, which facilitates assembly and maintenance of the whole complex.12 Mutations in the ARPC1B gene have been found to result in autosomal recessive syndrome of combined immune deficiency, impaired T-cell migration and proliferation and thrombocytopenia.13–15 Meanwhile, ARPC1B is correlated with malignant phenotypes of tumors such as melanoma, osteosarcoma, and oral squamous cell carcinoma.16–18 Unfortunately, there is no comprehensive report on ARPC1B in GBM. Toward this end, we set out to describe ARPC1B function in GBM-TAM regulating network. We further evaluated the impacts and mechanism in vitro using glioma cell lines and in vivo using orthotopic/subcutaneous GBM mouse models. These findings can provide new insight into GBM progression and provide a possible therapeutic target.