Src-family protein tyrosine kinase negatively regulates cerebellar long-term depression.
Protein phosphorylation is a major mechanism for the regulation of synaptic transmission. Previous studies have shown that several serine/threonine kinases are involved in the induction of long-term depression (LTD) at excitatory synapses on a Purkinje neuron (PN) in the cerebellum. Here, we show that Src-family protein tyrosine kinases (SFKs) are involved in the regulation of the LTD induction. Intracellular application of c-Src suppressed LTD. We also show that application of a SFK-selective inhibitor PP2 recovered LTD from the suppression caused by the inhibition of mGluR1 activity. These results indicate that SFKs negatively regulate the LTD induction at excitatory synapses on a cerebellar PN.
Tsuruno
Shun
S
Department of Biophysics, Graduate School of Science, Kyoto University, Kyoto 606-8502, Japan.
Kawaguchi
Shin-Ya
SY
Hirano
Tomoo
T
D000818:Animals; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology*; D002867:Chromones / Q000494:pharmacology; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D036881:Long-Term Synaptic Depression / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D011689:Purkinje Cells / Q000187:drug effects* / Q000502:physiology / Q000528:radiation effects; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism; D019061:src-Family Kinases / Q000494:pharmacology*
C117789:7-(hydroxyimino)cyclopropan(b)chromen-1a-carbxoylic acid ethyl ester; C412373:AG 1879; D002867:Chromones; D004791:Enzyme Inhibitors; D011743:Pyrimidines; D018094:Receptors, Metabotropic Glutamate; C104077:metabotropic glutamate receptor type 1; D014443:Tyrosine; D008734:Methoxyhydroxyphenylglycol; D019061:src-Family Kinases; C010117:3,4-dihydroxyphenylglycol