title: Ethanol-induced increase in Fyn kinase activity in the dorsomedial striatum is associated with subcellular redistribution of protein tyrosine phosphatase α.
abstract: In vivo exposure of rodents to ethanol leads to a long-lasting increase in Fyn kinase activity in the dorsomedial striatum (DMS). In this study, we set out to identify a molecular mechanism that contributes to the enhancement of Fyn activity in response to ethanol in the DMS. Protein tyrosine phosphatase α (PTPα) positively regulates the activity of Fyn, and we found that repeated systemic administration or binge drinking of ethanol results in an increase in the synaptic localization of PTPα in the DMS, the same site where Fyn resides. We also demonstrate that binge drinking of ethanol leads to an increase in Fyn activity and to the co-localization of Fyn and PTPα in lipid rafts in the DMS. Finally, we show that the level of tyrosine phosphorylated (and thus active) PTPα in the synaptic fractions is increased in response to contingent or non-contingent exposure of rats to ethanol. Together, our results suggest that the redistribution of PTPα in the DMS into compartments where Fyn resides is a potential mechanism by which the activity of the kinase is increased upon ethanol exposure. Such neuroadaptations could be part of a mechanism that leads to the development of excessive ethanol consumption.
authors.affiliation: Ernest Gallo Research Center, University of California San Francisco, Emeryville, California, USA.
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Gibb
authors.forename: Sami Ben
authors.initials: SB
authors.lastname: Hamida
authors.forename: Maria Fe
authors.initials: MF
authors.lastname: Lanfranco
authors.forename: Dorit
authors.initials: D
authors.lastname: Ron
mesh_terms: D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003342:Corpus Striatum / Q000187:drug effects* / Q000648:ultrastructure*; D000076122:Disks Large Homolog 4 Protein; D004305:Dose-Response Relationship, Drug; D004327:Drinking Behavior / Q000187:drug effects / Q000502:physiology; D004334:Drug Administration Schedule; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008297:Male; D021962:Membrane Microdomains / Q000187:drug effects / Q000201:enzymology; D008565:Membrane Proteins / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4 / Q000378:metabolism*
chemical_list: D002492:Central Nervous System Depressants; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C106354:flotillins; D000431:Ethanol; D050882:CREB-Binding Protein; C494365:Crebbp protein, rat; D054630:Receptor-Like Protein Tyrosine Phosphatases, Class 4