Synaptotagmin-like protein 1-3. A novel family of C-terminal-type tandem C2 proteins

Synaptotagmins (Syt), rabphilin-3A, and Doca belong to a family of carboxyl terminal type (C-type) tandem C2 proteins and are thought to be involved in vesicular trafficking. We have cloned and characterized a novel family of C-type tandem C2 proteins, designated Slp1-3 (synaptotagmin-like protein 1-3). The Slp1-3 C2 domains show high homology to granuphilin-a C2 domains, but the amino-terminal domain of Slp1-3 does not contain any known protein motifs or a transmembrane domain. A subcellular fractionation study indicated that Slp1-3 proteins are peripheral membrane proteins. Phospholipid binding experiments indicated that Slp3 is a Ca2+ dependent isoform, but Slp1 and Slp2 are Ca2+ independent isoforms, because only the Slp3 C2A domain showed Ca2+-dependent phospholipid binding activity. The C-terminus of Slp1-3 also bound neurexin I alpha in vitro, in the same manner as Syt family proteins, which may be important for the membrane association of Slp1-3. in addition, Slp family proteins are differentially distributed in different mouse tissues and at different developmental stages. (C) 2001 Academic Press.