Deficiency of a membrane skeletal protein, 4.1G, results in myelin abnormalities in the peripheral nervous system

We previously demonstrated that a membrane skeletal molecular complex, 4.1G–membrane palmitoylated protein 6 (MPP6)–cell adhesion molecule 4, is incorporated in Schwann cells in the peripheral nervous system (PNS). In this study, we evaluated motor activity and myelin ultrastructures in 4.1G-deficient (−/−) mice. When suspended by the tail, aged 4.1G−/− mice displayed spastic leg extension, especially after overwork. Motor-conduction velocity in 4.1G−/− mice was slower than that in wild-type mice. Using electron microscopy, 4.1G−/− mice exhibited myelin abnormalities: myelin was thicker in internodes, and attachment of myelin tips was distorted in some paranodes. In addition, we found a novel function of 4.1G for sorting a scaffold protein, Lin7, due to disappearance of the immunolocalization and reduction of the production of Lin7c and Lin7a in 4.1G−/− sciatic nerves, as well as the interaction of MPP6 and Lin7 with immunoprecipitation. Thus, we herein propose 4.1G functions as a signal for proper formation of myelin in PNS.