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 modulates 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 in decreased action-potential evoked Ca2+ responses. Additionally, we found that VAP-SCRN1 interactions play an important role in maintaining ER continuity and dynamics, as we

SUBMITTER: Ms. Feline, W Lindhout 

PROVIDER: S-SCDT-EMBOJ-2018-101345 | biostudies-other |

REPOSITORIES: biostudies-other