scholarly journals CSN6 and Rab34 Are Involved in Androgen Receptor Trafficking in Mouse Testicular Sertoli Cells

2018 ◽  
Vol 47 (6) ◽  
pp. 2360-2368 ◽  
Author(s):  
Qiong Deng ◽  
Chihua He ◽  
Yong Wu ◽  
Jianwen Zhang ◽  
Ying Zhang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Plasma Membrane ◽  
Androgen Receptor ◽  
Signaling Pathway ◽  
Sertoli Cells ◽  
Male Fertility ◽  
Receptor Trafficking ◽  
Cell Plasma Membrane ◽  
Physiological Concentration ◽  
Cell Plasma

Background/Aims: Androgen and its receptor (AR) play an important role in maintaining spermatogenesis and male fertility. Our previous studies showed that testosterone at a physiological concentration induces cytoplasmic AR translocation to the Sertoli cell plasma membrane of within 5 minutes. Methods: In this study, mass spectrometry (MS) and bioinformatic analyses were applied to identify candidate proteins mediating AR trafficking. The candidate proteins were knocked down by shRNA transfection. Results: Nine candidate proteins were identified by MS. The data was verified by co-immunoprecipitation and Western blot. Of the candidates, CSN6 regulated AR transport through the phosphorylation signaling pathway and Rab34 affected AR trafficking by regulating Ras activity. Conclusions: CSN6 and Rab34 are involved in AR trafficking by regulating the phosphorylation signaling pathway. These findings provide new insights into the testosterone signaling pathway in Sertoli cells that mediates spermatogenesis.

scholarly journals Vesicle-Associated Membrane Protein-Associated Protein A Is Involved in Androgen Receptor Trafficking in Mouse Sertoli Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Qiong Deng ◽  
Jianwen Zhang ◽  
Zhu Wang ◽  
Shengping Zhang ◽  
Fan Zhi ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Signaling Pathway ◽  
Sertoli Cells ◽  
Male Fertility ◽  
Protein A ◽  
Vesicle Transport ◽  
Receptor Trafficking ◽  
Nuclear Fraction ◽  
Caveolin 1 ◽  
Candidate Protein

Androgen and its receptor (AR) play an important role in maintaining spermatogenesis and male fertility. The nonclassical androgen signaling pathway is proposed to be mediated by an AR in plasma membrane in Sertoli cells. Our previous studies showed that testosterone induces cytoplasmic AR translocation to plasma membrane by binding with caveolin-1. This study was conducted to the underlying molecular mechanism mediating AR trafficking. Data from mass spectrometry using membrane coimmunoprecipitation sample by anti-AR antibody indicated VAPA is a candidate protein. Knockdown of VAPA by shRNA decreased the amount of AR localized to membrane and nuclear fraction and prevented AR trafficking after being exposed to testosterone. Further studies indicated AR trafficking in Sertoli cells might be mediated by VAPA via association with vesicle transport protein OSBP. This study can enrich the mechanism of the androgen actions and will be helpful for further clarifying the nonclassical signaling pathway of androgens in Sertoli cells.

scholarly journals Androgen Receptor Localizes to Plasma Membrane by Binding to Caveolin-1 in Mouse Sertoli Cells

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Qiong Deng ◽  
Yong Wu ◽  
Zeng Zhang ◽  
Yue Wang ◽  
Minghua Li ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Androgen Receptor ◽  
Signaling Pathway ◽  
Membrane Trafficking ◽  
Membrane Fraction ◽  
Cysteine Residue ◽  
Membrane Localization ◽  
Physiological Concentration ◽  
Caveolin 1 ◽  
New Evidence

The nonclassical androgen signaling pathway translates signals into alterations in cellular function within minutes, and this action is proposed to be mediated by an androgen receptor (AR) localized to the plasma membrane. This study was designed to determine the mechanism underlying the membrane association of androgen receptor in TM4 cells, a mouse Sertoli cell line. Western blot analysis indicated testosterone-induced AR translocation to the cell membrane. Data from coimmunoprecipitation indicated that AR is associated with caveolin-1, and testosterone enhanced this association. Knockdown of caveolin-1 by shRNA decreased the amount of AR localized to membrane fraction and prevented AR membrane trafficking after being exposed to testosterone at physiological concentration. The palmitoylation inhibitor 2-bromopalmitate decreased AR membrane localization in basal condition and completely blocked testosterone-induced AR translocation to membrane fraction. These data suggested that AR localized to membrane fraction by binding with caveolin-1 through palmitoylation of the cysteine residue. This study provided a new evidence for AR membrane localization and its application for clarifying the nonclassical signaling pathway of androgens.

Stimulation of Tumor-Specific Immunity Using Tumor Cell Plasma Membrane Antigen

Methods ◽  
1997 ◽  
Vol 12 (2) ◽  
pp. 155-164 ◽  
Author(s):  
Matthew F Mescher ◽  
Elena Savelieva
Keyword(s):  
Plasma Membrane ◽  
Tumor Cell ◽  
Cell Plasma Membrane ◽  
Specific Immunity ◽  
Cell Plasma ◽  
Stimulation Of

PROTEIN KINASE ACTIVITY ASSOCIATED WITH THE FAT CELL PLASMA MEMBRANE

1981 ◽  
Vol 9 (2) ◽  
pp. 232P-232P
Author(s):  
G. J. Belsham ◽  
R. W. Brownsey ◽  
R. M. Denton
Keyword(s):  
Plasma Membrane ◽  
Protein Kinase ◽  
Kinase Activity ◽  
Protein Kinase Activity ◽  
Fat Cell ◽  
Cell Plasma Membrane ◽  
Cell Plasma

Gastrointestinal Cell Plasma Membrane Wounding and Resealing In Vivo

1989 ◽  
Vol 96 (5) ◽  
pp. 1238-1248 ◽  
Author(s):  
Paul L. McNeil ◽  
Susumu Ito
Keyword(s):  
Plasma Membrane ◽  
Cell Plasma Membrane ◽  
Cell Plasma

scholarly journals A murine model of Charcot-Marie-Tooth disease 4F reveals a role for the C-terminus of periaxin in the formation and stabilization of Cajal bands

2018 ◽  
Vol 3 ◽  
pp. 20 ◽  
Author(s):  
Diane L. Sherman ◽  
Peter J. Brophy
Keyword(s):  
Plasma Membrane ◽  
Schwann Cell ◽  
Laminin Receptor ◽  
Cell Plasma Membrane ◽  
Charcot Marie Tooth ◽  
Charcot Marie Tooth Disease ◽  
C Terminus ◽  
Cell Plasma ◽  
Inherited Neuropathies ◽  
Tooth Disease

Charcot-Marie-Tooth (CMT) disease comprises up to 80 monogenic inherited neuropathies of the peripheral nervous system (PNS) that collectively result in demyelination and axon degeneration. The majority of CMT disease is primarily either dysmyelinating or demyelinating in which mutations affect the ability of Schwann cells to either assemble or stabilize peripheral nerve myelin. CMT4F is a recessive demyelinating form of the disease caused by mutations in the Periaxin (PRX) gene. Periaxin (Prx) interacts with Dystrophin Related Protein 2 (Drp2) in an adhesion complex with the laminin receptor Dystroglycan (Dag). In mice the Prx/Drp2/Dag complex assembles adhesive domains at the interface between the abaxonal surface of the myelin sheath and the cytoplasmic surface of the Schwann cell plasma membrane. Assembly of these appositions causes the formation of cytoplasmic channels called Cajal bands beneath the surface of the Schwann cell plasma membrane. Loss of either Periaxin or Drp2 disrupts the appositions and causes CMT in both mouse and man. In a mouse model of CMT4F, complete loss of Periaxin first prevents normal Schwann cell elongation resulting in abnormally short internodal distances which can reduce nerve conduction velocity, and subsequently precipitates demyelination. Distinct functional domains responsible for Periaxin homodimerization and interaction with Drp2 to form the Prx/Drp2/Dag complex have been identified at the N-terminus of Periaxin. However, CMT4F can also be caused by a mutation that results in the truncation of Periaxin at the extreme C-terminus with the loss of 391 amino acids. By modelling this in mice, we show that loss of the C-terminus of Periaxin results in a surprising reduction in Drp2. This would be predicted to cause the observed instability of both appositions and myelin, and contribute significantly to the clinical phenotype in CMT4F.

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