Journal of Cell Science ( IF 4 ) Pub Date : 2020-09-15 , DOI: 10.1242/jcs.247148 Alessandra Gallo 1, 2 , Lydia Danglot 1 , Francesca Giordano 3 , Bailey Hewlett 1 , Thomas Binz 4 , Christian Vannier 1 , Thierry Galli 5, 6
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.
中文翻译:
Sec22b-E-Syt复合体在神经突生长和分支中的作用。
亚历山德拉·加洛(Alessandra Gallo),莉迪亚·丹格(Lydia Danglot),弗朗西斯卡·佐丹奴(Francesca Giordano),贝利·休利特(Bailey Hewlett),托马斯·宾兹(Thomas Binz),克里斯蒂安·范尼尔(Christian Vannier)和蒂埃里·加利(Thierry Galli)
轴突和树突很长,通常是分支的神经突,在神经系统发育期间需要特别强烈的质膜(PM)扩展。神经突生长取决于内质网(ER)–PM接触处的非融合Sec22b–Stx1 SNARE复合物。在这里,我们显示Sec22b与ER脂质转移蛋白(LTP)的突触突触素(E-Syt)家族的成员相互作用,并且这种相互作用取决于Sec22b的longin域。E-Syts的过表达稳定了Sec22b-Stx1的关联,而E-Syts的沉默则相反。野生型E-Syt2的过表达,但不能转移脂质或不附着到ER的突变体,则增加了发育中神经元中轴突丝状伪足的形成和神经突的分支。梭菌神经毒素切割Stx1会抑制这种作用,Sec22b longin域和Sec22b突变体的表达,该突变体在SNARE和跨膜结构域之间具有扩展的接头。我们得出的结论是,Sec22b–Stx1 ER–PM接触位点通过与LTP(例如E-Syts)相互作用,促进了PM的扩增。
本文与论文的第一作者进行了第一人称访谈。