title: Transcriptional expression of myelin basic protein in oligodendrocytes depends on functional syntaxin 4: a potential correlation with autocrine signaling.
abstract: Myelination of axons by oligodendrocytes is essential for saltatory nerve conduction. To form myelin membranes, a coordinated synthesis and subsequent polarized transport of myelin components are necessary. Here, we show that as part of the mechanism to establish membrane polarity, oligodendrocytes exploit a polarized distribution of the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) machinery components syntaxins 3 and 4, localizing to the cell body and the myelin membrane, respectively. Our data further reveal that the expression of myelin basic protein (MBP), a myelin-specific protein that is synthesized "on site" after transport of its mRNA, depends on the correct functioning of the SNARE machinery, which is not required for mRNA granule assembly and transport per se. Thus, downregulation and overexpression of syntaxin 4 but not syntaxin 3 in oligodendrocyte progenitor cells but not immature oligodendrocytes impeded MBP mRNA transcription, thereby preventing MBP protein synthesis. The expression and localization of another myelin-specific protein, proteolipid protein (PLP), was unaltered. Strikingly, conditioned medium obtained from developing oligodendrocytes was able to rescue the block of MBP mRNA transcription in syntaxin 4-downregulated cells. These findings indicate that the initiation of the biosynthesis of MBP mRNA relies on a syntaxin 4-dependent mechanism, which likely involves activation of an autocrine signaling pathway.
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Bijlard
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Bert
authors.initials: B
authors.lastname: Klunder
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Jenny C
authors.initials: JC
authors.lastname: de Jonge
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Anita
authors.initials: A
authors.lastname: Nomden
authors.affiliation: Public Health Research Institute, Rutgers University, Newark, New Jersey, USA.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Tyagi
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Hans
authors.initials: H
authors.lastname: de Vries
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: Dick
authors.initials: D
authors.lastname: Hoekstra
authors.affiliation: Department of Cell Biology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands w.baron@umcg.nl.
authors.forename: Wia
authors.initials: W
authors.lastname: Baron
mesh_terms: D000818:Animals; D019898:Autocrine Communication / Q000235:genetics*; D001369:Axons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004622:Embryo, Mammalian; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D004676:Myelin Basic Protein / Q000235:genetics* / Q000378:metabolism; D018991:Myelin Proteolipid Protein / Q000235:genetics / Q000378:metabolism; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D061251:Primary Cell Culture; D050765:Qa-SNARE Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D014158:Transcription, Genetic
chemical_list: D017077:Culture Media, Conditioned; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D050765:Qa-SNARE Proteins; D012333:RNA, Messenger