CRMP4

The collapsin response-mediated protein 4 (CRMP-4) is a member of a family of proteins that are involved in axonal growth (Quinn et al., 1999). CRMP-4 protein is thought to be both cytosolic and membrane associated and is expressed transiently in post mitotic neurons, such as granule cells from the DG of the hippocampus (reviewed in Quinn et al., 1999).

The expression of CRMP-4 protein is regulated during development, reaching a peak approximately five days after birth, where maturation of the neurons occur, with a high rate of synaptic development. CRMP-4 has been shown to be expressed in the DG of adult rats in the early differentiation stage, and can be used to identify young, immature neurons (Quinn et al., 1999).

A number of genes involved in the regulation of axonal path finding and synapse formation have been identified so far. One such group is the CRMP group, a family of proteins that putatively function as intracellular signaling mediators that transduce signals related to axonal guidance (Quinn et al., 1999). Initial findings demonstrated that the chick protein, CRMP-62, was involved in the ability of collapsin, a member of the semaphorin family, to inhibit growth cone extension (Hedgecock et al., 1985).

CRMP-4 shares homology with the nematode gene, unc-33, mutations of which lead to aberrant patterns of axonal outgrowth (Hedgecock et al., 1985). Recent studies have identified several genes related to CRMP-62 in human brains (Hamajima et al., 1996). Four genes have been found in rat brains that are highly related to chick CRMP-62 (Wang and Strittmatter, 1996). In accordance with their presumed role in axonal guidance, these genes exhibit a relatively high degree of expression during development that decreases markedly in the postnatal period. CRMP-4 is expressed to a very limited extent in the adult brain (Wang and Strittmatter, 1996).

CRMP-4 immunohistochemistry has revealed that this protein is expressed transiently in post mitotic neurons during development (Minturn et al., 1995). Most importantly, CRMP-4 is expressed in newly generated cells in the SGZ, the SVZ, the olfactory bulbs, and the rostral migratory stream, areas in which the production or migration of neurons occurs in adulthood (figure 4).

However, it should be noted that CRMP-4 is also expressed in many other regions of the rat brain in which there is no record of adult neurogenesis or neuronal migration, e.g., in the olfactory glomeruli and in neurons of the cerebral cortex (Nacher et al., 2000).