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

Author(s):  
Naila Umer ◽  
Lena Arévalo ◽  
Sharang Phadke ◽  
Keerthika Lohanadan ◽  
Gregor Kirfel ◽  
...  

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.


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

1990 ◽  
Vol 38 (8) ◽  
pp. 1145-1153 ◽  
Author(s):  
J H Hartwig ◽  
D Brown ◽  
D A Ausiello ◽  
T P Stossel ◽  
L Orci

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.


PROTEOMICS ◽  
2017 ◽  
Vol 17 (13-14) ◽  
pp. 1700103 ◽  
Author(s):  
Jing Zhang ◽  
Shaohua Lu ◽  
Ye Zhou ◽  
Kun Meng ◽  
Zhipeng Chen ◽  
...  

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

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