Domain 3a mutation of VPS33A suppresses larval arrest phenotype in the loss of VPS45 in Caenorhabditis elegans

TL;DR

A mutation in the VPS33A protein can counteract the effects of losing VPS45 in C. elegans, revealing the importance of a specific protein domain in cellular processes.

Contribution

A novel mutation in VPS33A domain 3a is identified as a suppressor of VPS45 loss in C. elegans.

Findings

The VPS33A M376I mutation suppresses the temperature-sensitive lethality caused by VPS45 loss.

Domain 3a of VPS33A is essential for SNARE complex assembly and membrane fusion.

The results emphasize the functional significance of domain 3a in endosomal SM proteins.

Abstract

The Sec1/Munc18 (SM) protein VPS45 is a key regulator of SNARE-mediated membrane fusion in endosomal trafficking, but its precise role remains unknown. To understand the function of VPS45
in vivo
, we performed a genetic suppressor screen in
Caenorhabditis elegans
. We found that the temperature-sensitive lethality caused by the loss of
VPS-45
can be suppressed by a mutation in another SM protein, VPS33A. The VPS33A M376I mutation is located in domain 3a, which is predicted to be essential for SNARE complex assembly. These results highlight the functional importance of domain 3a in endosomal SM proteins and its role in specific membrane fusion.

Figures