RhoGAP18B isoforms act on distinct rho-family gtpases and regulate behavioral responses to alcohol via cofilin

Shamsideen A. Ojelade, Summer F. Acevedo, Geetha Kalahasti, Aylin R. Rodan, Adrian Rothenfluh

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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 ethanolinduced 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 Rho- GAP18B-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.

Original languageEnglish (US)
Article numbere0137465
JournalPLoS One
Volume10
Issue number9
DOIs
StatePublished - Sep 14 2015

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Actin Depolymerizing Factors
rho GTP-Binding Proteins
GTP Phosphohydrolases
guanosinetriphosphatase
Protein Isoforms
Ethanol
alcohols
ethanol
Alcohols
actin
Actins
sedation
GTPase-activating proteins
GTPase-Activating Proteins
Gene encoding
Cell Shape
alcohol abuse
Guanosine Triphosphate
Alcoholism
Drosophila

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

RhoGAP18B isoforms act on distinct rho-family gtpases and regulate behavioral responses to alcohol via cofilin. / Ojelade, Shamsideen A.; Acevedo, Summer F.; Kalahasti, Geetha; Rodan, Aylin R.; Rothenfluh, Adrian.

In: PLoS One, Vol. 10, No. 9, e0137465, 14.09.2015.

Research output: Contribution to journalArticle

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AU - Rodan, Aylin R.

AU - Rothenfluh, Adrian

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