Localized role of CRMP1 and CRMP2 in neurite outgrowth and growth cone steering

Abstract

Collapsin response mediator protein 1 (CRMP1) and CRMP2 have been known as mediators of extracellular guidance cues such as semaphorin 3A and contribute to cytoskeletal reorganization in the axonal pathfinding process. To date, how CRMP1 and CRMP2 focally regulate axonal pathfinding in the growth cone has not been elucidated. To delineate the local functions of these CRMPs, we carried out microscale-chromophore-assisted light inactivation (micro-CALI), which enables investigation of localized molecular functions with highly spatial and temporal resolutions. Inactivation of either CRMP1 or CRMP2 in the neurite shaft led to arrested neurite outgrowth. Micro-CALI of CRMP2 in the central domain of the growth cones consistently arrested neurite outgrowth, whereas micro-CALI of CRMP1 in the same region caused significant lamellipodial retraction, followed by retardation of neurite outgrowth. Focal inactivation of CRMP1 in its half region of the growth cone resulted in the growth cone turning away from the irradiated site. Conversely, focal inactivation of CRMP2 resulted in the growth cone turning toward the irradiated site. These findings suggest different functions for CRMP1 and CRMP2 in growth cone behavior and neurite outgrowth.

A functional coupling between CRMP1 and Nav1.7 for retrograde propagation of Semaphorin3A signaling

“…Thus our finding that CRMP2 is not required for the TTXsensitive axonal transport elicited by Sema3A, which is responsible for the localization of PlexA4 and TrkA in axons, is unexpected. Although the exact reasons are unknown, this is probably related to the different subcellular locations of CRMP1 and CRMP2 in neuronal cells (Higurashi et al, 2012;Makihara et al, 2016). We have previously conducted immunocytochemistry analyses by staining for the CRMPs with actin or tubulin (Higurashi et al, 2012).…”

“…Although the exact reasons are unknown, this is probably related to the different subcellular locations of CRMP1 and CRMP2 in neuronal cells (Higurashi et al, 2012;Makihara et al, 2016). We have previously conducted immunocytochemistry analyses by staining for the CRMPs with actin or tubulin (Higurashi et al, 2012). CRMP1 is uniformly localized throughout the growth cone with a subtle predominance in lamellipodia, and CRMP1 in the peripheral domain roughly colocalized with actin.…”

Collapsin Response Mediator Protein 4 Regulates Growth Cone Dynamics through the Actin and Microtubule Cytoskeleton

“…CRMP4 Regulates the Actin Cytoskeleton in Hippocampal Growth Cones-Although a population of CRMP1 and CRMP2 may also be distributed to actin-rich regions of the growth cone, the residues responsible for the F-actin bundling activity of CRMP4 are 35-59% identical to other CRMP family members and between 42 and 76% similar (23,55). Thus, actin bundling activity may be unique to CRMP4.…”

Regulation of dendritic development by semaphorin 3A through novel intracellular remote signaling

“…To answer these questions, the effects of local inactivation of CRMPs and other signaling molecules in a certain subcellular region such as growth cone, dendrite or cell body must be examined. 100 Estimation of membrane potential and local Ca 2C imaging will be required to elucidate the mechanism by which ion channel-coupled transport is elicited in response to Sema3A.…”