The septin Sept5/CDCrel-1 competes with α-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 α-SNAP, suggesting that Sept5 may regulate the availability of SNARE proteins through its interaction with syntaxin and the 7 S complex.

Prominent synaptic and metabolic abnormalities revealed by proteomic analysis of the dorsolateral prefrontal cortex in schizophrenia and bipolar disorder

“…78 Functionally, it has also been found that septin 5 binds to presynaptic SNARE complex proteins and inhibits exocytosis. 79,80 Indeed, many septins have been shown to have synaptic-associated binding partners which have been previously implicated in schizophrenia, for example syntaxin, complexin II and the microtubule-associated protein. [78][79][80] Septin 5 (also known as CDCrel-1 and Peanut-like 1) appears particularly interesting as it has been previously found to colocalize with GABAergic vesicles.…”

“…79,80 Indeed, many septins have been shown to have synaptic-associated binding partners which have been previously implicated in schizophrenia, for example syntaxin, complexin II and the microtubule-associated protein. [78][79][80] Septin 5 (also known as CDCrel-1 and Peanut-like 1) appears particularly interesting as it has been previously found to colocalize with GABAergic vesicles. 81 In a study investigating the distribution of septin 5 in the adult human brain, differential centrifugation revealed it to associate predominantly with neurons and to co-purify with SNAP-25 and synaptophysin marked synaptosomes.…”

Functional Genomic Analysis of Oligodendrocyte Differentiation

“…The high level of expression and upregulation of septin 5 (SEPT5) is of particular interest, because septins play important roles in directing polarized addition of membrane (Beites et al, 2005), suggesting that septin proteins may play a crucial role in myelination. Transmembrane protein 10 (TMEM10) is a mostly uncharacterized protein that is highly enriched in white matter and whose gene is upregulated 24-fold during OL differentiation (Table 1), making it a novel candidate CNS myelin protein.…”

Entry of Listeria monocytogenes in Mammalian Epithelial Cells: An Updated View

“…Among the many other cellular actin interacting partners, septins represent a group of small GTPases known to polymerize into oligomeric protein complexes and filaments (Surka et al 2002) that regulate cytokinesis, vesicle transport, and intracellular compartmentalization in a wide range of organisms (Beites et al 2005;Estey et al 2011). A member of the septin family, SEPT9, was initially identified as being recruited together with actin to the entry site of InlB-coated beads in LoVo cells (Pizarro-…”