Collapsin Response Mediator Proteins (collapsin + response_mediator_protein)

Distribution by Scientific Domains


Selected Abstracts


Calpain cleavage of collapsin response mediator proteins in ischemic mouse brain

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007
Susan X. Jiang
Abstract Collapsin response mediator proteins (CRMPs) are important brain-specific proteins with distinct functions in modulating growth cone collapse and axonal guidance during brain development. Our previous studies have shown that calpain cleaves CRMP3 in the adult mouse brain during cerebral ischemia [S.T. Hou et al. (2006) J. Neurosci., 26, 2241,2249]. Here, the expression of all CRMP family members (1,5) was examined in mouse brains that were subjected to middle cerebral artery occlusion. Among the five CRMPs, the expressions of CRMP1, CRMP3 and CRMP5 were the most abundant in the cerebral cortex and all CRMPs were targeted for cleavage by ischemia-activated calpain. Sub-cellular fractionation analysis showed that cleavage of CRMPs by calpain occurred not only in the cytoplasm but also in the synaptosomes isolated from ischemic brains. Moreover, synaptosomal CRMPs appeared to be at least one-fold more sensitive to cleavage compared with those isolated from the cytosolic fraction in an in-vitro experiment, suggesting that synaptosomal CRMPs are critical targets during cerebral ischemia-induced neuronal injury. Finally, the expression of all CRMPs was colocalized with TUNEL-positive neurons in the ischemic mouse brain, which further supports the notion that CRMPs may play an important role in neuronal death following cerebral ischemia. Collectively, these studies demonstrated that CRMPs are targets of calpains during cerebral ischemia and they also highlighted an important potential role that CRMPs may play in modulating ischemic neuronal death. [source]


Isolation and expression of a novel mitochondrial septin that interacts with CRMP/CRAM in the developing neurones

GENES TO CELLS, Issue 2 2003
Shusuke Takahashi
Background: Collapsin response mediator proteins (CRMPs) and CRAM belong to the unc-33 gene family which is implicated in axon guidance and outgrowth during neural development. However, their exact roles remain largely unknown. To understand the molecular basis of CRMP/CRAM function, we have undertaken to identify CRMP/CRAM interacting proteins. Results: We have identified a novel mitochondrial septin (M-septin) as one of the CRMP/CRAM interacting proteins from the developing rat brain. M-septin is a major, alternatively spliced variant of the H5 gene in developing mouse brain and its expression is up-regulated during the neuronal differentiation of embryonal carcinoma P19 cells. In COS-7 cells, M-septin is specifically localized to mitochondria whereas H5 is diffusely distributed to the perinuclear cytoplasm and plasma membranes. In contrast to H5, M-septin induces the mitochondrial translocation of CRAM but not CRMP2. Finally, M-Septin is found to be transiently translocated to mitochondria before the induction of the neurites and then dissociates from the mitochondria after neurite extension in P19 cells. Conclusions: Our results suggest that M-septin has a role which is distinct from H5, and together with CRMP/CRAM, may play an important role in the neuronal differentiation and axon guidance through the control of mitochondrial function. [source]


Regulatory machinery of UNC-33 Ce-CRMP localization in neurites during neuronal development in Caenorhabditis elegans

JOURNAL OF NEUROCHEMISTRY, Issue 6 2005
Daisuke Tsuboi
Abstract In Caenorhabditis elegans, unc-33 encodes an orthologue of the vertebrate collapsin response mediator protein (CRMP) family. We previously reported that CRMP-2 accumulated in the distal part of the growing axon of vertebrate neurons and played critical roles in axon elongation. unc-33 mutants show axonal outgrowth defects in several neurons. It has been reported that UNC-33 accumulates in neurites, whereas a missense mutation causes the mislocalization of UNC-33 from neurites to cell body, which suggests that the localization of UNC-33 in neurites is important for axonal outgrowth. However, it is unclear how UNC-33 accumulates in neurites and regulates neuronal development. In this study, to understand the regulatory mechanisms of localization of UNC-33 in neurites, we screened for the mutants that were involved in the localization of UNC-33, and identified three mutants: unc-14 (RUN domain protein), unc-51 (ULK kinase) and unc-116 (kinesin heavy chain). UNC-14 is known to associate with UNC-51. UNC-116 forms a complex with KLC-2 as Kinesin-1, a microtubule-dependent motor complex. We found that UNC-33 interacted with UNC-14 and KLC-2 in vivo. These results suggest that the UNC-14/UNC-51 complex and Kinesin-1 are involved in the localization of UNC-33 in neurites. [source]


Calpain cleavage of collapsin response mediator proteins in ischemic mouse brain

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 4 2007
Susan X. Jiang
Abstract Collapsin response mediator proteins (CRMPs) are important brain-specific proteins with distinct functions in modulating growth cone collapse and axonal guidance during brain development. Our previous studies have shown that calpain cleaves CRMP3 in the adult mouse brain during cerebral ischemia [S.T. Hou et al. (2006) J. Neurosci., 26, 2241,2249]. Here, the expression of all CRMP family members (1,5) was examined in mouse brains that were subjected to middle cerebral artery occlusion. Among the five CRMPs, the expressions of CRMP1, CRMP3 and CRMP5 were the most abundant in the cerebral cortex and all CRMPs were targeted for cleavage by ischemia-activated calpain. Sub-cellular fractionation analysis showed that cleavage of CRMPs by calpain occurred not only in the cytoplasm but also in the synaptosomes isolated from ischemic brains. Moreover, synaptosomal CRMPs appeared to be at least one-fold more sensitive to cleavage compared with those isolated from the cytosolic fraction in an in-vitro experiment, suggesting that synaptosomal CRMPs are critical targets during cerebral ischemia-induced neuronal injury. Finally, the expression of all CRMPs was colocalized with TUNEL-positive neurons in the ischemic mouse brain, which further supports the notion that CRMPs may play an important role in neuronal death following cerebral ischemia. Collectively, these studies demonstrated that CRMPs are targets of calpains during cerebral ischemia and they also highlighted an important potential role that CRMPs may play in modulating ischemic neuronal death. [source]


Axonal morphogenesis controlled by antagonistic roles of two CRMP subtypes in microtubule organization

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 11 2003
Junichi Yuasa-Kawada
Abstract During development, cells undergo dynamic morphological changes by rearrangements of the cytoskeleton including microtubules. However, molecular mechanisms underlying the microtubule remodeling between orientated and disoriented formations are almost unknown. Here we found that novel subtypes of collapsin response mediator proteins (CRMP-As) and the originals (CRMP-Bs), which occur from the alternative usage of different first coding exons, are involved in this conversion of microtubule patterns. Overexpression of CRMP2A and CRMP2B in chick embryonic fibroblasts induced orientated and disoriented patterns of microtubules, respectively. Moreover, sequential overexpression of another subtype overcame the effect of the former expression of the countersubtype. Overexpression experiments in cultured chick retinae showed that CRMP2B promoted axon branching and suppressed axon elongation of ganglion cells, while CRMP2A blocked these effects when co-overexpressed. Our findings suggest that the opposing activities of CRMP2A and CRMP2B contribute to the cellular morphogenesis including neuronal axonogenesis through remodeling of microtubule organization. [source]