Membrane Skeleton in Schmidt-Lanterman incisure in Schwann cells of the peripheral nervous system

Abstract

Schmidt-Lanterman incisure (SLI), a truncated cone-shape in a myelin internode, is a specific feature of myelinated nerve fibers in the peripheral nervous system (PNS). In this review, we focus on the membrane skeleton in SLI. First, we describe a membrane skeletal protein, 4.1G, and its relationship to membrane palmitoylated protein 6 (MPP6) and cell adhesion molecule 4 (CADM4), which is analogous to a molecular complex in the erythrocyte membrane skeleton, 4.1R-MPP1-glycophorin C. In 4.1G-deficient nerve fibers, the height of the SLI-truncated cones was reduced compared to that in the wild type. 4.1G was essential for molecular targeting of MPP6 and CADM4 in SLI. Second, we discuss a signal transduction protein, Src, in the SLIs of mouse sciatic nerves, and its phosphorylation states under normal conditions or deletion of 4.1G. Normally, Src is phosphorylated in Y527, but not in Y418. Developmentally, the phosphorylation in Y418 appeared in SLIs of early postnatal mouse sciatic nerves. An MPP6-Src interaction was found, and the phosphorylation of Y418 appeared in 4.1G-deficient nerve fibers. The functional meaning of the Src localization in SLI is discussed. Here, we demonstrate a novel Src-MPP6-4.1G-CADM4 membrane skeletal molecular complex in SLIs, with potential roles in regulation of adhesion and signal transduction in Schwann cells.