Handling Editor: Giampietro Schiavo
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 members of the extended synaptotagmin (E-Syt) family of ER lipid transfer proteins (LTPs), 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, and expression of the Sec22b longin domain and a Sec22b mutant with an extended linker between the 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.
This article has an associated First Person interview with the first author of the paper.
Footnotes
Competing interests
The authors declare no competing or financial interests.
Author contributions
Conceptualization: C.V., T.G.; Methodology: A.G., L.D., F.G., T.B., C.V.; Software: L.D.; Validation: T.G.; Formal analysis: F.G., B.H.; Investigation: A.G., L.D., F.G., B.H., C.V.; Data curation: A.G.; Writing - original draft: A.G., L.D., C.V., T.G.; Writing - review & editing: A.G., T.G.; Supervision: T.G.; Project administration: T.G.; Funding acquisition: T.G.
Funding
This work was funded by grants from the Association Française contre les Myopathies (Research Grant 16612), the French National Research Agency (Agence Nationale de la Recherche; NeuroImmunoSynapse ANR-13-BSV2-0018-02; MetDePaDi ANR-16-CE16-0012), the Institut National du Cancer (PLBIO 2018-149), the Fondation pour la Recherche Médicale (FRM), Who am I? Labex (Idex ANR-11-IDEX-0005-01), awards of the Association Robert Debré pour la Recherche Médicale and Fondation Bettencourt-Schueller, Idex USPC (‘Conventional And Unconventional Secretion In Neurite Growth’) to T.G.
Supplementary information
Supplementary information available online at https://jcs.biologists.org/lookup/doi/10.1242/jcs.247148.supplemental
- Received March 31, 2020.
- Accepted August 12, 2020.
- © 2020. Published by The Company of Biologists Ltd
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