Isolation and expression pattern of human Unc-33-like phosphoprotein 6/collapsin response mediator protein 5 (Ulip6/CRMP5): coexistence with Ulip2/CRMP2 in Sema3a- sensitive oligodendrocytes.
The Unc-33-like phosphoprotein/collapsin response mediator protein (Ulip/CRMP) family consists of four homologous phosphoproteins considered crucial for brain development. Autoantibodies produced against member(s) of this family by patients with paraneoplastic neurological diseases have made it possible to clone a fifth human Ulip/CRMP and characterize its cellular and anatomical distribution in developing brain. This protein, referred to as Ulip6/CRMP5, is highly expressed during rat brain development in postmitotic neural precursors and in the fasciculi of fibers, suggesting its involvement in neuronal migration/differentiation and axonal growth. In the adult, Ulip6/CRMP5 is still expressed in some neurons, namely in areas that retain neurogenesis and in oligodendrocytes in the midbrain, hindbrain, and spinal cord. Ulip2/CRMP2 and Ulip6/CRMP5 are coexpressed in postmitotic neural precursors at certain times during development and in oligodendrocytes in the adult. Because Ulip2/CRMP2 has been reported to mediate semaphorin-3A (Sema3A) signal in developing neurons, in studies to understand the function of Ulip6/CRMP5 and Ulip2/CRMP2 in the adult, purified adult rat brain oligodendrocytes were cultured in a Sema3A-conditioned medium. Oligodendrocytes were found to have Sema3A binding sites and to express neuropilin-1, the major Sema3A receptor component. In the presence of Sema3A, these oligodendrocytes displayed a dramatic reduction in process extension, which was reversed by removal of Sema3A and prevented by anti-neuropilin-1, anti-Ulip6/CRMP5, anti-Ulip2/CRMP2 antibodies, or VEGF-165, another neuropilin-1 ligand. These results indicate the existence in the adult brain of a Sema3A signaling pathway that modulates oligodendrocyte process extension mediated by neuropilin-1, Ulip6/CRMP5, and Ulip2/CRMP2, and they open new fields of investigation of neuron/oligodendrocyte interactions in the normal and pathological brain.
Ricard
D
D
Institut National de la Santé et de la Recherche Médicale U 433, Institut Fédératif des Neurosciences de Lyon, Hôpital Neurologique, 69003 Lyon, France.
Rogemond
V
V
Charrier
E
E
Aguera
M
M
Bagnard
D
D
Belin
M F
MF
Thomasset
N
N
Honnorat
J
J
D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D001921:Brain / Q000196:embryology / Q000254:growth & development / Q000378:metabolism; D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000494:pharmacology; D005260:Female; D006023:Glycoproteins / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D006867:Hydrolases; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines / Q000494:pharmacology; D008297:Male; D051379:Mice; D008869:Microtubule-Associated Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism; D039942:Neuropilin-1; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D040121:Semaphorin-3A; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D000906:Antibodies; D016228:Endothelial Growth Factors; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D040121:Semaphorin-3A; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; C095114:collapsin response mediator protein-2; D039942:Neuropilin-1; C415087:DPYSL5 protein, human; D006867:Hydrolases