title: The septin Sept5/CDCrel-1 competes with alpha-SNAP for binding to the SNARE complex.
abstract: SNARE (soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor) proteins are supposed to mediate the docking and/or fusion of the vesicle with the plasma membrane. However, it is not clearly understood how this process is regulated. In a search for potential SNARE regulators, we recently identified septin 5 (Sept5) as a novel SNARE interacting protein. Septins were first identified as filamentous proteins required for cytokinesis in yeast. Several septins have now been identified in mammals but little is known about their functions. We have previously shown that Sept5 is predominantly expressed in the brain, where it associates with vesicles and membranes through its interaction with the SNARE domain of syntaxin 1A. Furthermore, Sept5 appears to inhibit exocytosis, possibly by regulating vesicle targeting and/or fusion events. To gain insight into the role of Sept5, we have mapped the Sept5 domains important for syntaxin binding. We also investigated the ability of Sept5 to bind to syntaxin when in various protein complexes. Although Sept5 cannot bind an nSec1-syntaxin complex, it can bind syntaxin in a SNARE complex. This interaction is occluded by the binding of alpha-SNAP, suggesting that Sept5 may regulate the availability of SNARE proteins through its interaction with syntaxin and the 7 S complex.
authors.affiliation: Programme in Cell Biology, Hospital for Sick Children, 555 University Avenue, Toronto, Canada M5G 1X8.
authors.forename: Crestina L
authors.initials: CL
authors.lastname: Beites
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Campbell
authors.forename: William S
authors.initials: WS
authors.lastname: Trimble
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000502:physiology; D001921:Brain; D018797:Cell Cycle Proteins / Q000378:metabolism*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D046911:Macromolecular Substances / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011485:Protein Binding / Q000502:physiology; D050765:Qa-SNARE Proteins; D051381:Rats; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D050600:SNARE Proteins; D058112:Septins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D011994:Recombinant Proteins; D050600:SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; C494213:Stx1a protein, rat; D050827:Syntaxin 1; D033921:Vesicular Transport Proteins; D005982:Glutathione Transferase; C491613:Septin5 protein, rat; D058112:Septins