title: Sorting signals and regulation of cognate basolateral trafficking in myelin biogenesis.
abstract: A detailed understanding of trafficking pathways in mature oligodendrocytes is essential for addressing issues aimed at controlling (re)myelination by modulating myelin-directed transport. Previously, we have shown that viral marker proteins HA and VSV G, on reaching the apical and basolateral surfaces of polarized epithelial cells, respectively, are primarily transported to the plasma membrane and myelin sheet, respectively, in oligodendrocytes (OLGs). In the present study, we demonstrated that in OLGs basolateral sorting signals similar to those in epithelial cells may target proteins to the myelin sheet, emphasizing the basolateral- and apical-like nature of the myelin sheet and plasma membrane, respectively. Thus, substitution of essential amino acids reverses the direction of targeting of these proteins, whereas elimination of apical targeting of HA coincides with its dissipation from detergent-resistant microdomains. Furthermore, protein kinase C activation negatively regulated transport of the OLG resident transmembrane protein PLP to the myelin sheet, like that of VSV G as shown previously, but did not affect the localization of the membrane-associated myelin-specific proteins MBP and CNP. These data imply that several distinctly regulated pathways operate in myelin sheet directed-transport that at least partly rely on a cognate basolateral sorting signal.
authors.affiliation: University Medical Center Groningen, University of Groningen, Department of Cell Biology, Section of Membrane Cell Biology, Groningen, The Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: Klunder
authors.forename: Wia
authors.initials: W
authors.lastname: Baron
authors.forename: Cobi
authors.initials: C
authors.lastname: Schrage
authors.forename: Jenny
authors.initials: J
authors.lastname: de Jonge
authors.forename: Hans
authors.initials: H
authors.lastname: de Vries
authors.forename: Dick
authors.initials: D
authors.lastname: Hoekstra
mesh_terms: D000595:Amino Acid Sequence / Q000502:physiology; D019943:Amino Acid Substitution / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism* / Q000648:ultrastructure; D016764:Cell Polarity / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009836:Oligodendroglia / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D018991:Myelin Proteolipid Protein; D009419:Nerve Tissue Proteins; C489071:Plp1 protein, rat; D011493:Protein Kinase C