MISC

2002年4月

Cdk5/p35 regulates neurotransmitter release through phosphorylation and downregulation of P/Q-type voltage-dependent calcium channel activity

JOURNAL OF NEUROSCIENCE
  • K Tomizawa
  • ,
  • J Ohta
  • ,
  • M Matsushita
  • ,
  • A Moriwaki
  • ,
  • ST Li
  • ,
  • K Takei
  • ,
  • H Matsui

22
7
開始ページ
2590
終了ページ
2597
記述言語
英語
掲載種別
出版者・発行元
SOC NEUROSCIENCE

Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/ threonine kinase with close structural homology to the mitotic Cdks. The complex of Cdk5 and p35, the neuron-specific regulatory subunit of Cdk5, plays important roles in brain development, such as neuronal migration and neurite outgrowth. Moreover, Cdk5 is thought to be involved in the promotion of neurodegeneration in Alzheimer's disease.
Cdk5 is abundant in mature neurons; however, its physiological functions in the adult brain are unknown. Here we show that Cdk5/p35 regulates neurotransmitter release in the presynaptic terminal. Both Cdk5 and p35 were abundant in the synaptosomes. Roscovitine, a specific inhibitor of Cdk5 in neurons, induced neurotransmitter release from the synaptosomes in response to membrane depolarization and enhanced the EPSP slopes in rat hippocampal slices. The electrophysiological study using each specific inhibitor of the voltage-dependent calcium channels (VDCCs) and calcium imaging revealed that roscovitine enhanced Ca2+ influx from the P/Q-type VDCC. Moreover, Cdk5/p25 phosphorylated the intracellular loop connecting domains II and III (LII-III) between amino acid residues 724 and 981 of isoforms cloned from rat brain of the alpha(1A) subunit of P/Q-type Ca2+ channels. The phosphorylation inhibited the interaction of LII-III with SNAP-25 and synaptotagmin I, which were plasma membrane soluble N-ethylmaleimide- sensitive factor attachment protein (SNAP) receptor (SNARE) proteins and were required for efficient neurotransmitter release. These results strongly suggest that Cdk5/p35 inhibits neurotransmitter release through the phosphorylation of P/Q-type VDCC and downregulation of the channel activity.


リンク情報
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000174626000022&DestApp=WOS_CPL
ID情報
  • ISSN : 0270-6474
  • Web of Science ID : WOS:000174626000022

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