Modulation of the expression of GABA(A) receptors in rat cerebellar granule cells by protein tyrosine kinases and protein kinase C.
The expression of GABA(A) receptors in rat cerebellar granules in culture has been studied by beta(2/3) subunit immunocytochemistry and fluorescence confocal microscopy. These cells show labeling all over the cell bodies' plasma membrane and dendrites. Treatment with the protein tyrosine kinase (PTK) inhibitor genistein results in a decrease of the labeling associated with the beta(2/3) subunit in both cell bodies and dendrites. No effect was found with an inactive genistein analogue, daidzein. A similar effect was found with a protein kinase C (PKC) activator, phorbol myristate acetate (PMA). The effects of genistein and PMA are additive.The interpretation of the results is that PTK inhibition blocks exocytotic deposit of newly synthesized GABA(A) receptors onto the neuronal plasma membrane. On the other hand, PKC activation speeds up endocytotic removal of GABA(A) receptors.
Balduzzi
Raffaella
R
Unità INFM, Dipartimento di Fisica, Università di Genova, Via Dodecaneso 33, 16146 Genoa, Italy.
Cupello
Aroldo
A
Robello
Mauro
M
D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004705:Endocytosis / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D018613:Microscopy, Confocal; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism*; D021122:Protein Subunits; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D011963:Receptors, GABA-A / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
D004791:Enzyme Inhibitors; D021122:Protein Subunits; D011963:Receptors, GABA-A; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate