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Role of the Sec22b/E-Syt complex in neurite growth and ramification

Abstract : Axons and dendrites are long and often ramified neurites that need particularly intense plasma membrane (PM) expansion during the development of the nervous system. Neurite growth depends on non-fusogenic Sec22b-Stx1 SNARE complexes at endoplasmic reticulum (ER)-PM contacts. Here we show that Sec22b interacts with the endoplasmic reticulum lipid transfer proteins (LTPs) Extended-Synaptotagmins (E-Syts) and this interaction depends on the Longin domain of Sec22b. Overexpression of E-Syts stabilizes Sec22b-Stx1 association, whereas silencing of E-Syts has the opposite effect. Overexpression of wild-type E-Syt2, but not mutants unable to transfer lipids or attach to the ER, increase the formation of axonal filopodia and ramification of neurites in developing neurons. This effect is inhibited by a clostridial neurotoxin cleaving Stx1, expression of Sec22b Longin domain and a Sec22b mutant with extended linker between SNARE and transmembrane domains. We conclude that Sec22b-Stx1 ER-PM contact sites contribute to PM expansion by interacting with LTPs such as E-Syts.
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Submitted on : Friday, October 2, 2020 - 11:12:50 AM
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Gallo et al. . J Cell Sci. 202...
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Alessandra Gallo, Lydia Danglot, Francesca Giordano, Bailey Hewlett, Thomas Binz, et al.. Role of the Sec22b/E-Syt complex in neurite growth and ramification. Journal of Cell Science, Company of Biologists, 2020, ⟨10.1242/jcs.247148⟩. ⟨hal-02928155⟩

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