TRPM3 is expressed in sphingosine-responsive myelinating oligodendrocytes.
Oligodendrocytes are the myelin-forming cells of the CNS and guarantee proper nerve conduction. Sphingosine, one major component of myelin, has recently been identified to activate TRPM3, a member of the melastatin-related subfamily of transient receptor potential (TRP) channels. TRPM3 has been demonstrated to be expressed in brain with unknown cellular distribution. Here, we show for the first time that TRPM3 is expressed in oligodendrocytes in vitro and in vivo. TRPM3 is present during oligodendrocyte differentiation. Immunohistochemistry of adult rat brain slices revealed staining of white matter areas, which co-localized with oligodendrocyte markers. Analysis of the developmental distribution revealed that, prior to myelination, TRPM3 channels are localized on neurons. On oligodendrocytes they are found after the onset of myelination. RT-PCR studies showed that the transcription of TRPM3 splice variants is also developmentally regulated in vitro. Ca(2+) imaging approaches revealed the presence of a sphingosine-induced Ca(2+) entry mechanism in oligodendrocytes - with a pharmacological profile similar to the profile published for heterologously expressed TRPM3. These findings indicate that TRPM3 participates as a Ca(2+)-permeable and sphingosine-activated channel in oligodendrocyte differentiation and CNS myelination.
Hoffmann
Anja
A
Zelluläre Neurowissenschaften, Max-Delbrück-Centrum, Berlin, Germany.
Grimm
Christian
C
Kraft
Robert
R
Goldbaum
Olaf
O
Wrede
Arne
A
Nolte
Christiane
C
Hanisch
Uwe-Karsten
UK
Richter-Landsberg
Christiane
C
Brück
Wolfgang
W
Kettenmann
Helmut
H
Harteneck
Christian
C
D017398:Alternative Splicing / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D020013:Calcium Signaling / Q000235:genetics; D002463:Cell Membrane Permeability / Q000235:genetics; D006706:Homeostasis / Q000235:genetics; D009186:Myelin Sheath / Q000502:physiology*; D009457:Neuroglia / Q000378:metabolism / Q000502:physiology; D009836:Oligodendroglia / Q000378:metabolism*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D013110:Sphingosine / Q000502:physiology*; D050053:TRPM Cation Channels / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology
D050053:TRPM Cation Channels; C533867:TRPM3 protein, rat; D013110:Sphingosine