2019 Volume 31 Issue 180 Pages E63-E68
Glycosphingolipids that play crucial roles in various physiological contexts are ubiquitous components of the eukaryotic plasma membrane. Complex structures of glycan chains found in glycosphingolipids are accurately synthesized by glycosyltransferases including the GM3 and GM2 synthases in the Golgi apparatus. We have identified three isoforms of mouse GM3 synthase (M1-, M2-, and M3-GM3S), which have distinct lengths of an NH2-terminal cytoplasmic domain. These isoforms are co-expressed within a single cell, although they exhibit significant differences in their subcellular localization and protein stability. We have also found that GM2 synthase has two protein isoforms (M1- and M2-GM2S) with varying length of the NH2-terminal. Notably, M1-GM2S enhances the stability of M2-GM2S through disulfide-linked heterodimerization. These isoforms could participate in spatiotemporally fine regulation of the functions of GM3 and GM2 synthases and contribute to the maintenance of the balance of glycosphingolipid synthesis. This review summarizes our current understanding of regulatory mechanisms underlying the glycosphingolipid biosynthesis, particularly focusing on the intracellular dynamics and isoform production of GM3 and GM2 synthases.
