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The septin CDCrel-1 binds syntaxin and inhibits exocytosis

Abstract

Septins are GTPases required for the completion of cytokinesis in diverse organisms, yet their roles in cytokinesis or other cellular processes remain unknown. Here we describe studies of a newly identified septin, CDCrel-1, which is predominantly expressed in the nervous system. This protein was associated with membrane fractions, and a significant fraction of the protein copurified and coprecipitated with synaptic vesicles. In detergent extracts, CDCrel-1 and another septin, Nedd5, immunoprecipitated with the SNARE protein syntaxin by directly binding to syntaxin via the SNARE interaction domain. Transfection of HIT-T15 cells with wild-type CDCrel-1 inhibited secretion, whereas GTPase dominant-negative mutants enhanced secretion. These data suggest that septins may regulate vesicle dynamics through interactions with syntaxin.

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Figure 1: CDCrel-1 is predominantly expressed in the brain.
Figure 2: CDCrel-1 is associated with membranes and synaptic vesicles.
Figure 3: CDCrel-1 co-immunoprecipitates with Nedd5 and syntaxin.
Figure 4: CDCrel-1 directly binds to syntaxin 1A.
Figure 5: CDCrel-1 affects exocytosis.
Figure 6: CDCrel-1 and Nedd5 are predominantly associated with the membrane of PC12 cells and colocalize with syntaxin.

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Acknowledgements

The authors thank G. Boulianne for comments on the manuscript. This work was supported by grant MT-13465 from the Medical Research Council of Canada to WST and NIH grant AG13208 to RB.

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Correspondence to William S. Trimble.

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Beites, C., Xie, H., Bowser, R. et al. The septin CDCrel-1 binds syntaxin and inhibits exocytosis. Nat Neurosci 2, 434–439 (1999). https://doi.org/10.1038/8100

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