scholarly journals Regulation of TRPM8 channel activity by Src‐mediated tyrosine phosphorylation

2019 ◽  
Vol 235 (6) ◽  
pp. 5192-5203 ◽  
Author(s):  
Alexandra Manolache ◽  
Tudor Selescu ◽  
G. Larisa Maier ◽  
Mihaela Mentel ◽  
Aura Elena Ionescu ◽  
...  
2015 ◽  
Vol 208 (1) ◽  
pp. 89-107 ◽  
Author(s):  
Dimitra Gkika ◽  
Loic Lemonnier ◽  
George Shapovalov ◽  
Dmitri Gordienko ◽  
Céline Poux ◽  
...  

TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor–activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named “TRP channel–associated factors” (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity.


2014 ◽  
Vol 106 (2) ◽  
pp. 334a-335a
Author(s):  
Swapna Asuthkar ◽  
Lusine Demirkhanyan ◽  
Xiaohui Sun ◽  
Pia Elustondo ◽  
Kiran Velpula ◽  
...  

2018 ◽  
Vol 114 (3) ◽  
pp. 383a-384a
Author(s):  
Shanna Hamilton ◽  
Iuliia Polina ◽  
Radmila Terentyeva ◽  
Karim Roder ◽  
Tae Yun Kim ◽  
...  

2015 ◽  
Vol 37 (1) ◽  
pp. 98-104 ◽  
Author(s):  
Min Tang ◽  
Guang-yi Wu ◽  
Xin-zhong Dong ◽  
Zong-xiang Tang

2009 ◽  
Vol 284 (14) ◽  
pp. 9215-9224 ◽  
Author(s):  
Cruz Morenilla-Palao ◽  
María Pertusa ◽  
Víctor Meseguer ◽  
Hugo Cabedo ◽  
Félix Viana

2004 ◽  
Vol 279 (18) ◽  
pp. 18887-18894 ◽  
Author(s):  
Chihiro Hisatsune ◽  
Yukiko Kuroda ◽  
Kyoko Nakamura ◽  
Takafumi Inoue ◽  
Takeshi Nakamura ◽  
...  

2012 ◽  
Vol 353 (1-2) ◽  
pp. 68-74 ◽  
Author(s):  
Yevgen Yudin ◽  
Tibor Rohacs

2011 ◽  
Vol 22 (11) ◽  
pp. 1824-1835 ◽  
Author(s):  
Shoichiro Kanda ◽  
Yutaka Harita ◽  
Yoshio Shibagaki ◽  
Takashi Sekine ◽  
Takashi Igarashi ◽  
...  

Transient receptor potential canonicals (TRPCs) play important roles in the regulation of intracellular calcium concentration. Mutations in the TRPC6 gene are found in patients with focal segmental glomerulosclerosis (FSGS), a proteinuric disease characterized by dysregulated function of renal glomerular epithelial cells (podocytes). There is as yet no clear picture for the activation mechanism of TRPC6 at the molecular basis, however, and the association between its channel activity and pathogenesis remains unclear. We demonstrate here that tyrosine phosphorylation of TRPC6 induces a complex formation with phospholipase C (PLC)-γ1, which is prerequisite for TRPC6 surface expression. Furthermore, nephrin, an adhesion protein between the foot processes of podocytes, binds to phosphorylated TRPC6 via its cytoplasmic domain, competitively inhibiting TRPC6–PLC-γ1 complex formation, TRPC6 surface localization, and TRPC6 activation. Importantly, FSGS-associated mutations render the mutated TRPC6s insensitive to nephrin suppression, thereby promoting their surface expression and channel activation. These results delineate the mechanism of TRPC6 activation regulated by tyrosine phosphorylation, and imply the cell type–specific regulation, which correlates the FSGS mutations with deregulated TRPC6 channel activity.


2001 ◽  
Vol 120 (5) ◽  
pp. A168-A168
Author(s):  
T KAIHARA ◽  
T KUSAKA ◽  
H KAWAMATA ◽  
Y ODA ◽  
J IMURA ◽  
...  

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