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

• Published in: Journal of cell science Vol. 133; no. 18
• Main Authors: Gallo, Alessandra, Danglot, Lydia, Giordano, Francesca, Hewlett, Bailey, Binz, Thomas, Vannier, Christian, Galli, Thierry
• Format: Journal Article
• Language: English
• Published: England Company of Biologists 15.09.2020
• Subjects: Life Sciences; Membrane contact site; Membrane trafficking; Axonal growth; Filopodia; Lipid transfer protein; SNARE; Lipid-transfer protein
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.247148

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.