Phosphodiesterase-Ialpha/autotaxin's MORFO domain regulates oligodendroglial process network formation and focal adhesion organization.
Development of a complex process network by maturing oligodendrocytes is a critical but currently poorly characterized step toward myelination. Here, we demonstrate that the matricellular oligodendrocyte-derived protein phosphodiesterase-Ialpha/autotaxin (PD-Ialpha/ATX) and especially its MORFO domain are able to promote this developmental step. In particular, the single EF hand-like motif located within PD-Ialpha/ATX's MORFO domain was found to stimulate the outgrowth of higher order branches but not process elongation. This motif was also observed to be critical for the stimulatory effect of PD-Ialpha/ATX's MORFO domain on the reorganization of focal adhesions located at the leading edge of oligodendroglial protrusions. Collectively, our data suggest that PD-Ialpha/ATX promotes oligodendroglial process network formation and expansion via the cooperative action of multiple functional sites located within the MORFO domain and more specifically, a novel signaling pathway mediated by the single EF hand-like motif and regulating the correlated events of process outgrowth and focal adhesion organization.
Dennis
Jameel
J
Department of Anatomy and Neurobiology, Virginia Commonwealth University School of Medicine, Richmond, VA 23298, USA.
White
Michael A
MA
Forrest
Audrey D
AD
Yuelling
Larra M
LM
Nogaroli
Luciana
L
Afshari
Fatemah S
FS
Fox
Michael A
MA
Fuss
Babette
B
D000818:Animals; D000831:Animals, Newborn; D002450:Cell Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D022081:Cell Surface Extensions / Q000378:metabolism / Q000648:ultrastructure; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism*; D005260:Female; D022001:Focal Adhesions / Q000378:metabolism*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D010727:Phosphoric Diester Hydrolases / Q000737:chemistry / Q000378:metabolism*; D017434:Protein Structure, Tertiary / Q000502:physiology; D011755:Pyrophosphatases / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D000099189:Lysophospholipase D
D010727:Phosphoric Diester Hydrolases; D011755:Pyrophosphatases; D000099189:Lysophospholipase D