Myelin Proteolipid Protein (PLP), but Not DM-20, Is an Inositol Hexakisphosphate-binding Protein

Yoshihide Yamaguchi,Kazuhiro Ikenaka,Michio Niinobe,Hitoshi Yamada,Katsuhiko Mikoshiba

doi:10.1074/jbc.271.44.27838

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 (InsP6) significantly, not inositol 1,3,4,5-tetrakisphosphate. Most of the InsP6-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 InsP6 binding activity. These findings indicate that the PLP-specific domain confers the InsP6 binding activity and this interaction may be important for directing PLP transport to central nervous system myelin.

Highlights

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
We separated DM-20 from PLP by CM-52 chromatography and showed that DM-20 has no InsP6 binding activity. These findings indicate that the PLP-specific domain confers the InsP6 binding activity and this interaction may be important for directing PLP transport to central nervous system myelin

Summary

Introduction

Myelin proteolipid protein (PLP) and its alternatively spliced isoform, DM-20, are the major integral membrane proteins of central nervous system myelin. We separated DM-20 from PLP by CM-52 chromatography and showed that DM-20 has no InsP6 binding activity These findings indicate that the PLP-specific domain confers the InsP6 binding activity and this interaction may be important for directing PLP transport to central nervous system myelin. Eucaryotic cells are subdivided into membrane-bounded compartments These functional organelles contain sets of proteins and other molecules specific to themselves. A knowledge of this mechanism is essential for understanding how these compartments are created and maintained within eucaryotic cells The oligodendrocyte provides both an opportunity and a challenge for studying the machinery of intracellular vesicular transport. As expected for a protein being processed through the vesicular transport pathway, a significant lag exists between translation of PLP on the rough endoplasmic reticulum and its insertion into the myelin membrane (3, 7).

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Conclusion