Essential function of protein 4.1G in targeting of membrane protein palmitoylated 6 into Schmidt-Lanterman incisures in myelinated nerves.
Protein 4.1G is a membrane skeletal protein found in specific subcellular structures in myelinated Schwann cells and seminiferous tubules. Here, we show that in the mouse sciatic nerve, protein 4.1G colocalized at Schmidt-Lanterman incisures (SLI) and the paranodes with a member of the membrane-associated guanylate kinase (MAGUK) family, membrane protein palmitoylated 6 (MPP6). Coimmunoprecipitation experiments revealed that MPP6 was interacting with protein 4.1G. In contrast to wild-type nerves, in 4.1G knockout mice, MPP6 was found largely in the cytoplasm near Schwann cell nuclei, indicating an abnormal protein transport. Although the SLI remained in the 4.1G knockout sciatic nerves, as confirmed by E-cadherin immunostaining, their shape was altered in aged 4.1G knockout nerves compared to their shape in wild-type nerves. In the seminiferous tubules, MPP6 was localized similarly to protein 4.1G along cell membranes of the spermatogonium and early spermatocytes. However, in contrast to myelinated peripheral nerves, the specific localization of MPP6 in the seminiferous tubules was unaltered in the absence of protein 4.1G. These results indicate that 4.1G has a specific role in the targeting of MPP6 to the SLI and the assembly of these subcellular structures.
Department of Anatomy & Molecular Histology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Chuo City, Yamanashi, Japan. nobuot@shinshu-u.ac.jp
Nobuo
N
Terada
Yurika
Y
Saitoh
Nobuhiko
N
Ohno
Masayuki
M
Komada
Sei
S
Saitoh
Elior
E
Peles
Shinichi
S
Ohno
D000818:Animals; D017353:Gene Deletion; D051528:Guanylate Kinases / Q000032:analysis / Q000378:metabolism*; D058635:Lipid-Linked Proteins / Q000032:analysis / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008840:Microfilament Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D025941:Protein Interaction Mapping; D012584:Sciatic Nerve / Q000378:metabolism* / Q000648:ultrastructure*; D012671:Seminiferous Tubules / Q000378:metabolism / Q000648:ultrastructure
C540651:Epb4.1l2 protein, mouse; D058635:Lipid-Linked Proteins; C569941:MPP6 protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D051528:Guanylate Kinases