Regulation of syntaxin1A-munc18 complex for SNARE pairing in HEK293 cells

The Journal of Physiology
Svetlana E GladychevaEdward L Stuenkel

Abstract

The formation and dissolution of SNARE protein complexes is essential for Ca(2+)-triggered fusion of neurotransmitter-filled vesicles at the presynaptic membrane. Among the pre-synaptic SNARE proteins, the activation of the Q-SNARE syntaxin1A is a critical event for SNARE complex formation. Activation requires syntaxin1A to transit from a munc18-bound non-interacting state to one competent for SNARE binding. The molecular mechanisms that regulate this transition remain unclear. The propensity of syntaxin1A to promote voltage-dependent steady-state inactivation of N-type Ca(2+) channels and accelerate their entry into inactivation was used in a heterologous cell expression system to elucidate regulation of syntaxin1A protein-protein interactions. We report that coexpression of munc18 eliminated the promoting effect of syntaxin1A on inactivation. This effect of munc18 was completely disrupted by coexpression of munc13-1, but not munc13-2 or munc13-3. Also, since expression of munc13-1 with syntaxin1A resulted in an inactivation phenotype identical to that of munc18 with syntaxin1A, the action of munc13-1 on the munc18-syntaxin1A complex was functionally unique and did not result from competitive binding interactions. Furthermore,...Continue Reading

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Citations

Feb 19, 2011·The Journal of Biological Chemistry·Antionette L WilliamsEdward L Stuenkel
Jun 12, 2012·The Journal of Biological Chemistry·Eunjin OhDebbie C Thurmond
Jan 4, 2007·International Journal of Biological Sciences·Sunil K SaxenaConstantine George
Sep 13, 2008·Journal of Endocrinological Investigation·Q X YuanC Liu
Feb 26, 2013·Acta histochemica·Judyta Karolina JuranekJaroslaw Calka
Aug 20, 2009·Immunology·Nicola J Topham, Eric W Hewitt
Oct 19, 2004·The Journal of Biological Chemistry·Jiang LiuEdward L Stuenkel
Sep 27, 2005·Physiological Reviews·Susumu Seino, Tadao Shibasaki
Jun 5, 2007·The Journal of Biological Chemistry·Svetlana E GladychevaEdward L Stuenkel

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