Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings

Rongqing Shuang, Lin Zhang, Angus Fletcher, Guy E. Groblewski, Jonathan A. Pevsner, Edward L. Stuenkel

Research output: Contribution to journalArticle

Abstract

The Munc-18-syntaxin 1A complex has been postulated to act as a negative control on the regulated exocytotic process because its formation blocks the interaction of syntaxin with vesicle SNARE proteins. However, the formation of this complex is simultaneously essential for the final stages of secretion as evidenced by the necessity of Munc-18's homologues in Saccharomyces cerevisiae (Sec1p), Drosophila (ROP), and Caenorhabditis elegans (Unc-18) for proper secretion in these organisms. As such, any event that regulates the interaction of these two proteins is important for the control of secretion. One candidate for such regulation is cyclin-dependent kinase 5 (Cdk5), a member of the Cdc2 family of cell division cycle kinases that has recently been copurified with Munc-18 from rat brain. The present study shows that Cdk5 bound to its neural specific activator p35 not only binds to Munc-18 but utilizes it as a substrate for phosphorylation. Furthermore, it is demonstrated that Munc-18 that has been phosphorylated by Cdk5 has a significantly reduced affinity for syntaxin 1A. Finally, it is shown that Cdk5 can also bind to syntaxin 1A and that a complex of Cdk5, p35, Munc-18, and syntaxin 1A can be fashioned in the absence of ATP and promptly disassembled upon the addition of ATP. These results suggest a model in which p35-activated Cdk5 becomes localized to the Munc-18-syntaxin 1A complex by its affinity for both proteins so that it may phosphorylate Munc-18 and thus permit the positive interaction of syntaxin 1A with upstream protein effectors of the secretory mechanism.

Original languageEnglish (US)
Pages (from-to)4957-4966
Number of pages10
JournalJournal of Biological Chemistry
Volume273
Issue number9
DOIs
StatePublished - Feb 27 1998

Fingerprint

Syntaxin 1
Cyclin-Dependent Kinase 5
Nerve Endings
Adenosine Triphosphate
Qa-SNARE Proteins
SNARE Proteins
Phosphorylation
Proteins
Caenorhabditis elegans
Yeast
Drosophila
Saccharomyces cerevisiae
Rats
Brain
Cell Cycle
Phosphotransferases
Cells
Substrates

ASJC Scopus subject areas

  • Biochemistry

Cite this

Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings. / Shuang, Rongqing; Zhang, Lin; Fletcher, Angus; Groblewski, Guy E.; Pevsner, Jonathan A.; Stuenkel, Edward L.

In: Journal of Biological Chemistry, Vol. 273, No. 9, 27.02.1998, p. 4957-4966.

Research output: Contribution to journalArticle

Shuang, Rongqing ; Zhang, Lin ; Fletcher, Angus ; Groblewski, Guy E. ; Pevsner, Jonathan A. ; Stuenkel, Edward L. / Regulation of Munc-18/syntaxin 1A interaction by cyclin-dependent kinase 5 in nerve endings. In: Journal of Biological Chemistry. 1998 ; Vol. 273, No. 9. pp. 4957-4966.
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