Collapsin Response Mediator Proteins (CRMPs): Involvement in Nervous System Development and Adult Neurodegenerative Disorders

Abstract

The members of the collapsin response mediator protein (CRMP) family-five cytosolic phosphoproteins -are highly expressed throughout brain development. The first member to be cloned, CRMP2, was identified as an intracellular messenger required for the growth cone-collapse induced by semaphorin 3A (Sema3A). A rapidly expanding body of study indicates that the functions of CRMPs are not solely limited to the signaling transduction of the Sema3A guidance cue. They are probably involved in multiple cellular and molecular events involved in apoptosis/proliferation, cell migration, and differentiation. In the adult brain, the expression of CRMPs is dramatically downregulated. However, they remain expressed in structures that retain their capacity for differentiation and plasticity and also in a subpopulation of oligodendrocytes (CRMP2 and CRMP5). Moreover, the expression of CRMPs is altered in neurodegenerative diseases, and these proteins may be of key importance in the physiopathology of the adult nervous system.

Collapsin Response Mediator Proteins (CRMPs) Are a New Class of Microtubule-associated Protein (MAP) That Selectively Interacts with Assembled Microtubules via a Taxol-sensitive Binding Interaction

“…CRMPs are abundant proteins that exist as cytosolic tetramers (14,29,30), of which CRMP2 is the best studied as an essential mediator of growth cone collapse induced by Sema3A signaling (2, 3). CRMP2 itself accumulates in growth cones and also promotes multiple axons when ectopically overexpressed (21,31).…”

Systematic interaction network filtering identifies CRMP1 as a novel suppressor of huntingtin misfolding and neurotoxicity

“…By applying sequential interaction network filtering, we defined 13 HTT-associated human proteins whose expression in the caudate nucleus of HD patient brains is likely to be abnormal. Evaluation of available data and focused confirmation studies enabled the discovery of the protein collapsin response mediator protein 1 (CRMP1), a neuron-specific phosphoprotein that plays a central role in neuronal development and communication (Charrier et al 2003). Levels of CRMP1 transcription were abnormally low in the brains of HD patients.…”

Amino- and carboxyl-terminal domains of Filamin-A interact with CRMP1 to mediate Sema3A signalling

“…Among five members of CRMP mammalian homologues (CRMP1-5) 9 , at least CRMP1 and CRMP2 are involved in Sema3A signalling 10 . Mutant mice analysis showed that crmp1 genetically interacts with sema3a in the dendritic and synaptic development of the cortical neurons 11 .…”