A role for the syntaxin N-terminus

UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology

Publication Date


Document Type



Animals; Models, Molecular; Munc18 Proteins; Protein Binding; Qa-SNARE Proteins; Synaptic Transmission


Life Sciences | Medicine and Health Sciences


Intracellular membrane fusion steps in eukaryotes require the syntaxin family of SNARE (soluble N-ethylmaleimide-sensitive fusion protein-attachment protein receptor) proteins. Syntaxins are regulated at several levels through interactions with regulatory proteins, including the SM (Sec1p/Munc18) proteins. Key to understanding this regulation is the characterization of different SM-syntaxin binding interactions at the molecular level and in terms of their contribution to function in vivo. The most conserved SM-syntaxin binding mode is through interaction of the syntaxin's extreme N-terminal peptide with a hydrophobic pocket on the surface of the SM protein. Surprisingly, mutant versions of two different SM proteins abrogated for this binding display no discernable phenotypes in vivo. In this issue of the Biochemical Journal, Johnson et al. demonstrate that loss of the N-terminal binding interaction between the syntaxin UNC-64 and the SM protein UNC-18 severely impairs neuromuscular synaptic transmission in Caenorhabditis elegans, resulting in an unco-ordinated phenotype. In contrast, loss of a second mode of SM-syntaxin binding has no detectable effect. Collectively, these results suggest that, although different membrane trafficking steps are all regulated by SM-syntaxin interactions using similar binding modes, they are differentially regulated, highlighting the need for careful dissection of the binding modes.

DOI of Published Version



Biochem J. 2009 Feb 15;418(1):e1-3. Link to article on publisher's site

Journal/Book/Conference Title

The Biochemical journal

Related Resources

Link to Article in PubMed

PubMed ID