scholarly journals Environmental toxicants perturb human Sertoli cell adhesive function via changes in F-actin organization mediated by actin regulatory proteins

2014 ◽  
Vol 29 (6) ◽  
pp. 1279-1291 ◽  
Author(s):  
X. Xiao ◽  
D. D. Mruk ◽  
E. I. Tang ◽  
C. K. C. Wong ◽  
W. M. Lee ◽  
...  
Keyword(s):  
Sertoli Cell ◽  
Regulatory Proteins ◽  
Environmental Toxicants ◽  
Actin Organization ◽  
Cell Adhesive ◽  
Actin Regulatory Proteins

scholarly journals Perfluorooctanesulfonate (PFOS) Perturbs Male Rat Sertoli Cell Blood-Testis Barrier Function by Affecting F-Actin Organization via p-FAK-Tyr407: An in Vitro Study

Endocrinology ◽  
2014 ◽  
Vol 155 (1) ◽  
pp. 249-262 ◽  
Author(s):  
Hin-Ting Wan ◽  
Dolores D. Mruk ◽  
Chris K. C. Wong ◽  
C. Yan Cheng
Keyword(s):  
Tight Junction ◽  
Sertoli Cell ◽  
Sertoli Cells ◽  
Connexin 43 ◽  
Male Rat ◽  
Environmental Toxicants ◽  
Adhesion Proteins ◽  
Actin Organization ◽  
Blood Testis Barrier

Environmental toxicants such as perfluorooctanesulfonate (PFOS) have been implicated in male reproductive dysfunction, including reduced sperm count and semen quality, in humans. However, the underlying mechanism(s) remains unknown. Herein PFOS at 10–20 μM (∼5–10 μg/mL) was found to be more potent than bisphenol A (100 μM) in perturbing the blood-testis barrier (BTB) function by disrupting the Sertoli cell tight junction-permeability barrier without detectable cytotoxicity. We also delineated the underlying molecular mechanism by which PFOS perturbed Sertoli cell BTB function using an in vitro model that mimics the BTB in vivo. First, PFOS perturbed F-actin organization in Sertoli cells, causing truncation of actin filaments at the BTB. Thus, the actin-based cytoskeleton was no longer capable of supporting the distribution and/or localization of actin-regulatory and adhesion proteins at the cell-cell interface necessary to maintain BTB integrity. Second, PFOS was found to perturb inter-Sertoli cell gap junction (GJ) communication based on a dye-transfer assay by down-regulating the expression of connexin-43, a GJ integral membrane protein. Third, phosphorylated focal adhesion kinase (FAK)-Tyr407 was found to protect the BTB from the destructive effects of PFOS as shown in a study via an overexpression of an FAK Y407E phosphomimetic mutant. Also, transfection of Sertoli cells with an FAK-specific microRNA, miR-135b, to knock down the expression of phosphorylated FAK-Tyr407 was found to worsen PFOS-mediated Sertoli cell tight junction disruption. In summary, PFOS-induced BTB disruption is mediated by down-regulating phosphorylated FAK-Tyr407 and connexin-43, which in turn perturbed F-actin organization and GJ-based intercellular communication, leading to mislocalization of actin-regulatory and adhesion proteins at the BTB.

scholarly journals Ena/VASP regulates mDia2-initiated filopodial length, dynamics, and function

2014 ◽  
Vol 25 (17) ◽  
pp. 2604-2619 ◽  
Author(s):  
Melanie Barzik ◽  
Leslie M. McClain ◽  
Stephanie L. Gupton ◽  
Frank B. Gertler
Keyword(s):  
Molecular Mechanisms ◽  
Cell Spreading ◽  
Model System ◽  
Regulatory Proteins ◽  
Signaling Cascades ◽  
Cellular Functions ◽  
Actin Organization ◽  
Actin Regulatory Proteins ◽  
Dynamics And Function ◽  
And Function

Filopodia are long plasma membrane extensions involved in the formation of adhesive, contractile, and protrusive actin-based structures in spreading and migrating cells. Whether filopodia formed by different molecular mechanisms equally support these cellular functions is unresolved. We used Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP)–deficient MVD7 fibroblasts, which are also devoid of endogenous mDia2, as a model system to investigate how these different actin regulatory proteins affect filopodia morphology and dynamics independently of one another. Filopodia initiated by either Ena/VASP or mDia2 contained similar molecular inventory but differed significantly in parameters such as number, length, F-actin organization, lifetime, and protrusive persistence. Moreover, in the absence of Ena/VASP, filopodia generated by mDia2 did not support initiation of integrin-dependent signaling cascades required for adhesion and subsequent lamellipodial extension, thereby causing a defect in early cell spreading. Coexpression of VASP with constitutively active mDia2M/A rescued these early adhesion defects. We conclude that Ena/VASP and mDia2 support the formation of filopodia with significantly distinct properties and that Ena/VASP regulates mDia2-initiated filopodial morphology, dynamics, and function.

LPS induces phosphorylation of actin-regulatory proteins leading to actin reassembly and macrophage motility

2011 ◽  
Vol 113 (1) ◽  
pp. 80-92 ◽  
Author(s):  
Galyna Kleveta ◽  
Kinga Borzęcka ◽  
Mykola Zdioruk ◽  
Maciej Czerkies ◽  
Hanna Kuberczyk ◽  
...  
Keyword(s):  
Regulatory Proteins ◽  
Actin Regulatory Proteins

scholarly journals Loss of Profilin3 Impairs Spermiogenesis by Affecting Acrosome Biogenesis, Autophagy, Manchette Development and Mitochondrial Organization

2021 ◽  
Vol 9 ◽  
Author(s):  
Naila Umer ◽  
Lena Arévalo ◽  
Sharang Phadke ◽  
Keerthika Lohanadan ◽  
Gregor Kirfel ◽  
...  
Keyword(s):  
Actin Polymerization ◽  
Regulatory Proteins ◽  
Autophagic Flux ◽  
Nuclear Fraction ◽  
Rna Seq ◽  
Head Shape ◽  
Male Factor ◽  
Protein Levels ◽  
Acrosome Formation ◽  
Actin Regulatory Proteins

Profilins (PFNs) are key regulatory proteins for the actin polymerization in cells and are encoded in mouse and humans by four Pfn genes. PFNs are involved in cell mobility, cell growth, neurogenesis, and metastasis of tumor cells. The testes-specific PFN3 is localized in the acroplaxome–manchette complex of developing spermatozoa. We demonstrate that PFN3 further localizes in the Golgi complex and proacrosomal vesicles during spermiogenesis, suggesting a role in vesicle transport for acrosome formation. Using CRISPR/Cas9 genome editing, we generated mice deficient for Pfn3. Pfn3–/– males are subfertile, displaying a type II globozoospermia. We revealed that Pfn3–/– sperm display abnormal manchette development leading to an amorphous sperm head shape. Additionally, Pfn3–/– sperm showed reduced sperm motility resulting from flagellum deformities. We show that acrosome biogenesis is impaired starting from the Golgi phase, and mature sperm seems to suffer from a cytoplasm removal defect. An RNA-seq analysis revealed an upregulation of Trim27 and downregulation of Atg2a. As a consequence, mTOR was activated and AMPK was suppressed, resulting in the inhibition of autophagy. This dysregulation of AMPK/mTOR affected the autophagic flux, which is hallmarked by LC3B accumulation and increased SQSTM1 protein levels. Autophagy is involved in proacrosomal vesicle fusion and transport to form the acrosome. We conclude that this disruption leads to the observed malformation of the acrosome. TRIM27 is associated with PFN3 as determined by co-immunoprecipitation from testis extracts. Further, actin-related protein ARPM1 was absent in the nuclear fraction of Pfn3–/– testes and sperm. This suggests that lack of PFN3 leads to destabilization of the PFN3–ARPM1 complex, resulting in the degradation of ARPM1. Interestingly, in the Pfn3–/– testes, we detected increased protein levels of essential actin regulatory proteins, cofilin-1 (CFL1), cofilin-2 (CFL2), and actin depolymerizing factor (ADF). Taken together, our results reveal the importance for PFN3 in male fertility and implicate this protein as a candidate for male factor infertility in humans.

scholarly journals miR-149 represses metastasis of hepatocellular carcinoma by targeting actin-regulatory proteins PPM1F

Oncotarget ◽  
2015 ◽  
Vol 6 (35) ◽  
pp. 37808-37823 ◽  
Author(s):  
Gang Luo ◽  
Ya-Ling Chao ◽  
Bo Tang ◽  
Bo-Sheng Li ◽  
Yu-Feng Xiao ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Regulatory Proteins ◽  
Actin Regulatory Proteins

scholarly journals Helix Straightening as an Activation Mechanism in the Gelsolin Superfamily of Actin Regulatory Proteins

2009 ◽  
Vol 284 (32) ◽  
pp. 21265-21269 ◽  
Author(s):  
Hui Wang ◽  
Sakesit Chumnarnsilpa ◽  
Anantasak Loonchanta ◽  
Qiang Li ◽  
Yang-Mei Kuan ◽  
...  
Keyword(s):  
Regulatory Proteins ◽  
Activation Mechanism ◽  
Actin Regulatory Proteins

scholarly journals Polarization of gelsolin and actin binding protein in kidney epithelial cells.

1990 ◽  
Vol 38 (8) ◽  
pp. 1145-1153 ◽  
Author(s):  
J H Hartwig ◽  
D Brown ◽  
D A Ausiello ◽  
T P Stossel ◽  
L Orci
Keyword(s):  
Plasma Membrane ◽  
Epithelial Cells ◽  
Water Permeability ◽  
Collecting Duct ◽  
Regulatory Proteins ◽  
Actin Binding ◽  
Apical Plasma Membrane ◽  
Actin Binding Protein ◽  
Principal Cells ◽  
Actin Regulatory Proteins

Vasopressin regulates transepithelial osmotic water permeability in the kidney collecting duct and in target cells in other tissues. In the presence of hormone, water channels are inserted into an otherwise impermeable apical plasma membrane and the apical surface of these cells is dramatically remodelled. Because cytochalasin B and D greatly reduce the response of these cells to vasopressin, actin filaments are believed to participate in the events leading to an increase in transepithelial water permeability. Modulation of the actin filamentous network requires the concerted action of specific actin regulatory proteins, and in the present study we used protein A-gold immunocytochemistry to localize two important molecules, gelsolin and actin binding protein (ABP), in epithelial cells of the kidney inner medulla. Gelsolin and, to a lesser extent, ABP were concentrated in clusters in the apical cell web of principal cells of the collecting duct. Aggregates of gold particles were often associated with the cytoplasmic side of plasma membrane regions forming surface extensions or microvilli. The basolateral plasma membrane was labeled to a much lesser extent than the apical plasma membrane. In the thin limbs of Henle, ABP was localized over the apical plasma membrane in ascending limbs, but gelsolin labeling was weak in these cells. In thin descending limbs, the pattern of labeling was completely reversed, with abundant apical gelsolin labeling but only weak ABP immunolabeling. Although the significance of the distribution of actin regulatory proteins in thin limbs is unknown, the abundance and the predominantly apical polarization of both ABP and gelsolin in principal cells of the collecting duct is consistent with a role of the actin cytoskeleton in the mechanism of vasopressin actin.

The modular structure of actin-regulatory proteins

1998 ◽  
Vol 10 (1) ◽  
pp. 23-34 ◽  
Author(s):  
Yoram A Puius ◽  
Nicole M Mahoney ◽  
Steven C Almo
Keyword(s):  
Modular Structure ◽  
Regulatory Proteins ◽  
Actin Regulatory Proteins
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