RhoGAP18B Isoforms Act on Distinct Rho-Family GTPases and Regulate Behavioral Responses to Alcohol via Cofilin

被引：12

作者：

Ojelade, Shamsideen A. ^{[1
,2
]}

Acevedo, Summer F. ^{[1
]}

Kalahasti, Geetha ^{[1
]}

Rodan, Aylin R. ^{[3
]}

Rothenfluh, Adrian ^{[1
,2
]}

机构：

[1] Univ Texas SW Med Ctr Dallas, Dept Psychiat, Dallas, TX 75390 USA

[2] Univ Texas SW Med Ctr Dallas, Program Neurosci, Dallas, TX 75390 USA

[3] Univ Texas SW Med Ctr Dallas, Dept Internal Med, Div Nephrol, Dallas, TX 75390 USA

来源：

PLOS ONE | 2015年 / 10卷 / 09期

关键词：

LOW-LEVEL; ETHANOL; DROSOPHILA; CYTOSKELETON; CONSUMPTION; DYNAMICS; CELLS; EPS8; RAC; MECHANISMS;

D O I：

10.1371/journal.pone.0137465

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Responses to the effects of ethanol are highly conserved across organisms, with reduced responses to the sedating effects of ethanol being predictive of increased risk for human alcohol dependence. Previously, we described that regulators of actin dynamics, such as the Rho-family GTPases Rac1, Rho1, and Cdc42, alter Drosophila's sensitivity to ethanol-induced sedation. The GTPase activating protein RhoGAP18B also affects sensitivity to ethanol. To better understand how different RhoGAP18B isoforms affect ethanol sedation, we examined them for their effects on cell shape, GTP-loading of Rho-family GTPase, activation of the actin-severing cofilin, and actin filamentation. Our results suggest that the RhoGAP18B-PA isoform acts on Cdc42, while PC and PD act via Rac1 and Rho1 to activate cofilin. In vivo, a loss-of-function mutation in the cofilin-encoding gene twinstar leads to reduced ethanol-sensitivity and acts in concert with RhoGAP18B. Different RhoGAP18B isoforms, therefore, act on distinct subsets of Rho-family GTPases to modulate cofilin activity, actin dynamics, and ethanol-induced behaviors.

引用

页数：17