Mutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity.

ABSTRACT: Mutations in the Golgi SNARE (SNAP [soluble NSF attachment protein] receptor) protein Membrin (encoded by the GOSR2 gene) cause progressive myoclonus epilepsy (PME). Membrin is a ubiquitous and essential protein mediating ER-to-Golgi membrane fusion. Thus, it is unclear how mutations in Membrin result in a disorder restricted to the nervous system. Here, we use a multi-layered strategy to elucidate the consequences of Membrin mutations from protein to neuron. We show that the pathogenic mutations cause partial reductions in SNARE-mediated membrane fusion. Importantly, these alterations were sufficient to profoundly impair dendritic growth in Drosophila models of GOSR2-PME. Furthermore, we show that Membrin mutations cause fragmentation of the presynaptic cytoskeleton coupled with transsyna

SUBMITTER: Praschberger R 

PROVIDER: S-EPMC5640804 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature