VAP-SCRN1 interaction regulates dynamic endoplasmic reticulum remodeling and presynaptic function.

ABSTRACT: In neurons, the continuous and dynamic endoplasmic reticulum (ER) network extends throughout the axon, and its dysfunction causes various axonopathies. However, it remains largely unknown how ER integrity and remodeling modulate presynaptic function in mammalian neurons. Here, we demonstrated that ER membrane receptors VAPA and VAPB are involved in modulating the synaptic vesicle (SV) cycle. VAP interacts with secernin-1 (SCRN1) at the ER membrane via a single FFAT-like motif. Similar to VAP, loss of SCRN1 or SCRN1-VAP interactions resulted in impaired SV cycling. Consistently, SCRN1 or VAP depletion was accompanied by decreased action potential-evoked Ca²⁺ responses. Additionally, we found that VAP-SCRN1 interactions play an important role in maintaining ER continuity and dynam

SUBMITTER: Lindhout FW 

PROVIDER: S-EPMC6792018 | biostudies-literature | 2019 Oct

REPOSITORIES: biostudies-literature