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

Abstract

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, antiUlip6/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.

CRMP5 (Collapsin Response Mediator Protein 5) Regulates Dendritic Development and Synaptic Plasticity in the Cerebellar Purkinje Cells

“…In the cerebellar Purkinje cells, CRMP5 expression is observed in adult mice (Ricard et al, 2001;Bretin et al, 2005). At P14, the cells surrounding the Purkinje cells were positively stained with anti-CRMP5 antibody, while signal was absent in the Purkinje cell in crmp5 ϩ/ Ϫ mice (Fig.…”

Semaphorin3A Signaling Mediated by Fyn-dependent Tyrosine Phosphorylation of Collapsin Response Mediator Protein 2 at Tyrosine 32

“…CRMP2 is expressed in oligodendrocyte and neurons. Sema3A-induced branching of oligodendrocytes is blocked by anti-CRMP2 antibody (23). In addition, Fyn has been implicated in myelination (24).…”

High CRMP2 expression in peripheral T lymphocytes is associated with recruitment to the brain during virus-induced neuroinflammation

“…Cells were then re-suspended in PBS at 4°C awaiting analysis (if surface staining alone was required) or processed further for intracellular CRMP2 protein detection. For the latter, cells were re-suspended in PBS containing 0.5% saponin (permeabilization buffer -PB) and incubated for 30 min at RT with rabbit anti-peptide4/CRMP2 antibody, prepared against a CRMP2 (Ricard et al, 2001). The cells were washed once with PBS 0.05% saponin and then incubated in PBS 0.5% saponin with fluorescein isothiocyanate (FITC)-labeled goat F(ab')2 antirabbit for 20 min at RT.…”