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

Khazaei, Mohamad; Girouard, Marie-Pier; Alchini, Ricardo; Tone, Stephan Ong; Shimada, Tadayuki; Bechstedt, Susanne; Cowan, Mitra; Guillet, Dominique; Wiseman, Paul W.; Brouhard, Gary J.; Cloutier, Jasmin; Fournier, Alyson E.

doi:10.1074/jbc.m114.570440

Cited by 58 publications

(83 citation statements)

References 56 publications

(65 reference statements)

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“…The CRMP proteins regulate cell movements in response to extracellular cues such as Semaphorin 3A (37), but they do not hydrolyze pyrimidine (38). The majority of work on CRMP proteins thus far has focused on CRMP-2 and its ability to modulate microtubule dynamics by binding to tubulin dimers (19,20,39,40), but evidence has been accumulating that CRMP proteins also regulate the actin cytoskeleton (31,(41)(42)(43)(44)(45). Our demonstration here that CRMP-1 promotes Arp2/3-dependent assembly of Listeria actin comet tails opens the possibility that CRMP-1 might also contribute to the assembly of Arp2/3-dependent actin networks in uninfected cells.…”

Section: Discussionmentioning

confidence: 99%

Collapsin Response Mediator Protein-1 Regulates Arp2/3-dependent Actin Assembly

Yu-Kemp

Brieher

2016

Journal of Biological Chemistry

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Listeria monocytogenes is a bacterial parasite that uses host proteins to assemble an Arp2/3-dependent actin comet tail to power its movement through the host cell. Initiation of comet tail assembly is more efficient in cytosol than it is under defined conditions, indicating that unknown factors contribute to the reaction. We therefore fractionated cytosol and identified CRMP-1 as a factor that facilitates Arp2/3-dependent Listeria actin cloud formation in the presence of Arp2/3 and actin alone. It also scored as an important factor for Listeria actin comet tail formation in brain cytosol. CRMP-1 does not nucleate actin assembly on its own, nor does it directly activate the Arp2/3 complex. Rather, CRMP-1 scored as an auxiliary factor that promoted the ability of Listeria ActA protein to activate the Arp2/3 complex to trigger actin assembly. CRMP-1 is one member of a family of five related proteins that modulate cell motility in response to extracellular signals. Our results demonstrate an important role for CRMP-1 in Listeria actin comet tail formation and open the possibility that CRMP-1 controls cell motility by modulating Arp2/3 activation.

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Section: Discussionmentioning

confidence: 99%

Collapsin Response Mediator Protein-1 Regulates Arp2/3-dependent Actin Assembly

Yu-Kemp

Brieher

2016

Journal of Biological Chemistry

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“…Tissue structure abnormalities and neuronal hyperactivity due to the enhanced dendritic growth of mitral cells in the olfactory bulb was also observed in Crmp4−/− mice [58,59]. Likewise, a decrease in axon growth of hippocampal neurons was also seen in Crmp4−/− mice [60]. Analyses of Crmp5−/− mice revealed atrophy of the Purkinje cell bodies and dendrites, leading to the loss of LTD and motor coordination [34].…”

Section: Crmps In Neural Circuit Formationmentioning

confidence: 89%

“…Crmp4-/-Increased proximal bifurcation of CA1 pyramidal neurons [57] Axon growth and motor and sensory recovery after SCI [41,88] Enhanced dendritic growth and hyperactivity in olfactory bulb neurons [58,59] Reduced apoptosis, inflammation, and scar formation [41] Decrease in axon extension and growth cone formation [60] Delayed dopaminergic neuron death in the PD model [43] …”

Section: Crmps In Neuronal Degeneration and Regenerationmentioning

confidence: 99%

CRMPs Function in Neurons and Glial Cells: Potential Therapeutic Targets for Neurodegenerative Diseases and CNS Injury

2016

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Neurodegeneration in the adult mammalian central nervous system (CNS) is fundamentally accelerated by its intrinsic neuronal mechanisms, including its poor regenerative capacity and potent extrinsic inhibitory factors. Thus, the treatment of neurodegenerative diseases faces many obstacles. The degenerative processes, consisting of axonal/dendritic structural disruption, abnormal axonal transport, release of extracellular factors, and inflammation, are often controlled by the cytoskeleton. From this perspective, regulators of the cytoskeleton could potentially be a therapeutic target for neurodegenerative diseases and CNS injury. Collapsin response mediator proteins (CRMPs) are known to regulate the assembly of cytoskeletal proteins in neurons, as well as control axonal growth and neural circuit formation. Recent studies have provided some novel insights into the roles of CRMPs in several inhibitory signaling pathways of neurodegeneration, in addition to its functions in neurological disorders and CNS repair. Here, we summarize the roles of CRMPs in axon regeneration and its emerging functions in non-neuronal cells, especially in inflammatory responses. We also discuss the direct and indirect targeting of CRMPs as a novel therapeutic strategy for neurological diseases.

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“…While it has been assumed that MTs play an instructive role in the regulation of growth cone protrusion (Mack et al, 2000;Koester et al, 2007;Khazaei et al, 2014), no direct evidence has been provided as to whether and how MTs regulate edge membrane dynamics during growth cone guidance. Here, we report that polymerizing MTs toward the growth cone's leading edge induce localized lamellipodial protrusion by providing VAMP7-positive vesicles to the membrane.…”

Section: Discussionmentioning

confidence: 99%

“…cAMP may promote MT extension by activating protein kinase A (PKA), which phosphorylates stathmin and inhibits stathmin-mediated tubulin sequestration (Grenningloh et al, 2004). PKA can also facilitate MT growth via phosphorylation of glycogen synthase kinase 3␤, which regulates MT-associating proteins, such as collapsin response mediator protein 2 and adenomatous polyposis coli (Shelly et al, 2010;Kim et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Cyclic Nucleotide Control of Microtubule Dynamics for Axon Guidance

et al. 2016

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Graded distribution of intracellular second messengers, such as Ca 2ϩ and cyclic nucleotides, mediates directional cell migration, including axon navigational responses to extracellular guidance cues, in the developing nervous system. Elevated concentrations of cAMP or cGMP on one side of the neuronal growth cone induce its attractive or repulsive turning, respectively. Although effector processes downstream of Ca 2ϩ have been extensively studied, very little is known about the mechanisms that enable cyclic nucleotides to steer migrating cells. Here, we show that asymmetric cyclic nucleotide signaling across the growth cone mediates axon guidance via modulating microtubule dynamics and membrane organelle transport. In embryonic chick dorsal root ganglion neurons in culture, contact of an extending microtubule with the growth cone leading edge induces localized membrane protrusion at the site of microtubule contact. Such a contact-induced protrusion requires exocytosis of vesicle-associated membrane protein 7 (VAMP7)-positive vesicles that have been transported centrifugally along the microtubule. We found that the two cyclic nucleotides counteractively regulate the frequency of microtubule contacts and targeted delivery of VAMP7 vesicles: cAMP stimulates and cGMP inhibits these events, thereby steering the growth cone in the opposite directions. By contrast, Ca 2ϩ signals elicit no detectable change in either microtubule contacts or VAMP7 vesicle delivery during Ca 2ϩ -induced growth cone turning. Our findings clearly demonstrate growth cone steering machinery downstream of cyclic nucleotide signaling and highlight a crucial role of dynamic microtubules in leading-edge protrusion for cell chemotaxis.

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

Cited by 58 publications

References 56 publications

Collapsin Response Mediator Protein-1 Regulates Arp2/3-dependent Actin Assembly

Collapsin Response Mediator Protein-1 Regulates Arp2/3-dependent Actin Assembly

CRMPs Function in Neurons and Glial Cells: Potential Therapeutic Targets for Neurodegenerative Diseases and CNS Injury

Cyclic Nucleotide Control of Microtubule Dynamics for Axon Guidance

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