Myelin proteolipid protein (PLP), but not DM-20, is an inositol hexakisphosphate-binding protein

Abstract

Myelin proteolipid protein (PLP) and its alternatively spliced isoform, DM-20, are the major integral membrane proteins of central nervous system myelin. It is known that PLP and DM-20 are delivered to myelin by a finely regulated vesicular transport system in oligodendrocytes. Evolutionarily, it is believed that ancestral DM-20 acquired a PLP-specific exon to create PLP, after which PLP/DM-20 became a major component of central nervous system myelin. We purified PLP as an inositol 1,3,4,5-tetrakisphosphate-binding protein after solubilization in a non-organic solvent. However, under the isotonic condition, PLP binds inositol hexakisphosphate (InsP 6) significantly, not inositol 1,3,4,5-tetrakisphosphate. Most of the InsP 6- binding proteins are involved in vesicular transport, suggesting the involvement of PLP in vesicular transport. We separated DM-20 from PLP by CM- 52 chromatography and showed that DM-20 has no InsP 6 binding activity. These findings indicate that the PLP-specific domain confers the InsP 6 binding activity and this interaction may be important for directing PLP transport to central nervous system myelin.