title: Ethanol increases p190RhoGAP activity, leading to actin cytoskeleton rearrangements.
abstract: We previously reported that cells chronically exposed to ethanol show alterations in actin cytoskeleton organization and dynamics in primary cultures of newborn rat astrocytes, a well-established in vitro model for foetal alcohol spectrum disorders. These alterations were attributed to a decrease in the cellular levels of active RhoA (RhoA-GTP), which in turn was produced by an increase in the total RhoGAP activity. We here provide evidence that p190RhoGAPs are the main factors responsible for such increase. Thus, in astrocytes chronically exposed to ethanol we observe: (i) an increase in p190A- and p190B-associated RhoGAP activity; (ii) a higher binding of p190A and p190B to RhoA-GTP; (iii) a higher p120RasGAP-p190A RhoGAP complex formation; and (iv) the recruitment of both p190RhoGAPs to the plasma membrane. The simultaneous silencing of both p190 isoforms prevents the actin rearrangements and the total RhoGAP activity increase triggered both by ethanol. Therefore, our data directly points p190RhoGAPs as ethanol-exposure molecular targets on glial cells of the CNS.
authors: Departament de Biologia Cellular, Immunologia i Neurociències, Facultat de Medicina, and Instituts d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS) i de Nanociències i Nanotecnologia (IN2UB), Universitat de Barcelona, Barcelona, Spain.
authors: Javier
authors: J
authors: Selva
authors: Gustavo
authors: G
authors: Egea
mesh_terms: D000199:Actins / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002478:Cells, Cultured; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000166:cytology; D003599:Cytoskeleton / Q000378:metabolism*; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans; D047468:Immunoprecipitation; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D014162:Transfection
chemical_list: D000199:Actins; C513040:Arhgap35 protein, rat; D002492:Central Nervous System Depressants; D034741:RNA, Small Interfering; D012097:Repressor Proteins; D000431:Ethanol