Rtn4a promotes exocytosis in mammalian cells while ER morphology does not necessarily affect exocytosis and translation

Abstract

ER tubules and sheets conventionally correspond to smooth and rough ER, respectively. The ratio of ER tubules-to-sheets varies in different cell types and changes in response to cellular conditions, potentially impacting the functional output of the ER. To directly test if ER morphology impacts ER function, we increased the tubule-to-sheet ratio by Rtn4a overexpression and monitored effects on protein translation and trafficking. While expression levels of several cell surface and secreted proteins were unchanged, their exocytosis was increased. Rtn4a depletion reduced cell surface trafficking without affecting ER morphology, and increasing the tubule-to-sheet ratio by other means did not affect trafficking. These data suggest that Rtn4a enhances exocytosis independently of changes in ER morphology. We demonstrate that Rtn4a enhances ER-to-Golgi trafficking and co-localizes with COPII vesicles. We propose that Rtn4a promotes COPII vesicle formation by inducing membrane curvature. Taken together, we show that altering ER morphology does not necessarily affect protein synthesis or trafficking, but that Rtn4a specifically enhances exocytosis.