Involvement of membrane skeletal molecules in the Schmidt–Lanterman incisure in Schwann cells

Abstract

Membrane skeletal networks form a two-dimensional lattice structure beneath erythrocyte membranes. 4.1R-MPP (membrane palmitoylated protein) 1-glycophorin C is one of the basic molecular complexes of the membrane skeleton. An analogous molecular complex, 4.1G-MPP6-cell adhesion molecule 4 (CADM4), is incorporated into the Schmidt-Lanterman incisure (SLI), a truncated cone shape in the myelin internode that is a specific feature of myelinated nerve fibers formed in Schwann cells in the peripheral nervous system. In this review, the dynamic structure of peripheral nerve fibers under stretching conditions is demonstrated using in vivo cryotechnique. The structures of nerve fibers had a beaded appearance, and the heights of SLI circular-truncated cones increased at the narrow sites of nerve fibers under the stretched condition. The height of SLI-truncated cones was lower in 4.1G-deficient nerve fibers than in wild-type nerve fibers. 4.1G was essential for the molecular targeting of MPP6 and CADM4 in SLI. The signal transduction protein, Src, was also involved in the 4.1G-MPP6-CADM4 molecular complex. The phosphorylation of Src was altered by the deletion of 4.1G. Thus, we herein demonstrate a membrane skeletal molecular complex in SLI that has potential roles in the regulation of adhesion and signal transduction as well as in structural stability in Schwann cells.

Not Just Another Scaffolding Protein Family: The Multifaceted MPPs

“…Tseng et al observed that MPP6 might be involved in the assembly of Lin-7 protein complexes in epithelial and neuronal cells. Indeed, further studies confirmed that MPP6 and Lin-7 form, as already mentioned, a molecular complex with CADM4 and 4.1G in mouse peripheral neurons [84,[99][100][101][102]. In MPP6-deficient mice, Lin-7 expression was downregulated and absent in SLIs in Schwann cells, thus indicating MPP6 as a regulator of Lin-7 expression and localization.…”

“…An example of a protein complex, similar to those previously described, was discovered in mouse sciatic nerves, where MPP6 was found in the complex with protein 4.1G, Lin-7 (a MAGUK protein, which is described below in more detail) and another member of the Necl family (CADM4) [84,[99][100][101][102]. Immunostaining studies of MPP6 and CADM4 showed that, analogously to 4.1G, they can be found at the cell membrane of Schmidt-Lanterman incisures (SLIs) and paranodes [84,99].…”

Age-Dependent Increase in Schmidt-Lanterman Incisures and a Cadm4-Associated Membrane Skeletal Complex in Fatty Acid 2-hydroxylase Deficient Mice: a Mouse Model of Spastic Paraplegia SPG35

“…The differences between PNS myelin proteomes of Fa2h +/+ and Fa2h −/− mice were small in all age groups examined, and upon focusing on well-established myelin proteins, we observed a rather specific increase of the four proteins Cadm4, Mpp6 (Pals2), Lin7, and band 4.1G (Epb41l2). These four molecules are co-regulated at the protein and mRNA level [ 29 ], and there is clear evidence that they form a complex in SLIs [ 32 , 36 – 38 ]. Localization of this complex in SLIs depends on band 4.1G protein [ 39 ].…”

In focus in HCB

“…Terada's group has been studying the role of membrane protein complexes in the formation of myelin sheaths in mouse peripheral nervous system (Terada et al 2016;Saitoh et al 2017). In a recent publication (Saitoh et al 2017) using 4.1G-deficient mice, these authors demonstrated that the 4.1G protein component of the skeletal molecular complex 4.1G-membrane palmitoylated protein 6 (MMP6)-Lin7-cell adhesion molecule 4 (CADM4) functions as a signaling molecule for the proper formation of Schwann cell-associated myelin.…”