Analysis of Scfd2 - A New Member of the SM Protein Family

Abstract

Proteins of the SM (Sec1/Munc18) protein family are indispensable regulators of vesicle fusion in eukaryotic cells. Currently, four basic types of SM proteins are known: Sec1 or Munc18, Sly1, Vps45 and Vps33. In different trafficking steps, they interact with respective SNARE (soluble N-ethylmaleimide-sensitive factor attachment receptor) proteins, which catalyze the fusion of vesicle and target membranes by zippering into a tight four-helix bundle between membranes. Most SM proteins interact directly with the Qa-SNARE or syntaxin, although different binding modes have been proposed. Upon phylogenetic analysis of the SM protein family, we came across a new member of the family, named Scfd2 (Sec1 Family Domain Containing 2). Although it is likely that this new SM protein type was present in the genome of the last eukaryotic common ancestor, it has only been maintained in certain lineages, among them most animals and plants. It is absent, however, from several widely used model organisms like S. cerevisiae, C. elegans and Drosophila. Little is known about the function of Scfd2 and it is not clear whether it acts in vesicle trafficking in a manner comparable to other SM proteins and whether it has a specific SNARE binding partner. Recent data suggest that Scfd2 may interact or even be a part of a tethering complex involved in ER-Golgi transport. In order to shed light on the function of Scfd2, we are investigating its interaction with the key proteins involved in ER-Golgi trafficking, using biochemical approaches.