title: A role for the syntaxin N-terminus.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA 01605, USA. mary.munson@umassmed.edu
authors.forename: Mary
authors.initials: M
authors.lastname: Munson
authors.forename: Nia J
authors.initials: NJ
authors.lastname: Bryant
mesh_terms: D000818:Animals; D008958:Models, Molecular; D051938:Munc18 Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding; D050765:Qa-SNARE Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009435:Synaptic Transmission
chemical_list: D051938:Munc18 Proteins; D050765:Qa-SNARE Proteins