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/CR MP) family consists of four homologous phosphoproteins considered crucial f or brain development. Autoantibodies produced against member(s) of this fam ily by patients with paraneoplastic neurological diseases have made it poss ible to clone a fifth human Ulip/CRMP and characterize its cellular and ana tomical distribution in developing brain. This protein, referred to as Ulip 6/CRMP5, is highly expressed during rat brain development in postmitotic ne ural precursors and in the fasciculi of fibers, suggesting its involvement in neuronal migration/differentiation and axonal growth. In the adult, Ulip 6/CRMP5 is still expressed in some neurons, namely in areas that retain neu rogenesis and in oligodendrocytes in the midbrain, hindbrain, and spinal co rd. Ulip2/CRMP2 and Ulip6/CRMP5 are coexpressed in postmitotic neural precu rsors at certain times during development and in oligodendrocytes in the ad ult. Because Ulip2/CRMP2 has been reported to mediate semaphorin-3A (Sema3A ) signal in developing neurons, in studies to understand the function of Ul ip6/CRMP5 and Ulip2/CRMP2 in the adult, purified adult rat brain oligodendr ocytes were cultured in a Sema3A-conditioned medium. Oligodendrocytes were found to have Sema3A binding sites and to express neuropilin-1, the major S ema3A 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, an ti-Ulip2/CRMP2 antibodies, or VEGF-165, another neuropilin-1 ligand. These results indicate the existence in the adult brain of a Sema3A signaling pat hway that modulates oligodendrocyte process extension mediated by neuropili n-1, Ulip6/CRMP5, and Ulip2/CRMP2, and they open new fields of investigatio n of neuron/oligodendrocyte interactions in the normal and pathological bra in.