title: Mapping CRMP3 domains involved in dendrite morphogenesis and voltage-gated calcium channel regulation.
abstract: Although hippocampal neurons are well-distinguished by the morphological characteristics of their dendrites and their structural plasticity, the mechanisms involved in regulating their neurite initiation, dendrite growth, network formation and remodeling are still largely unknown, in part because the key molecules involved remain elusive. Identifying new dendrite-active cues could uncover unknown molecular mechanisms that would add significant understanding to the field and possibly lead to the development of novel neuroprotective therapy because these neurons are impaired in many neuropsychiatric disorders. In our previous studies, we deleted the gene encoding CRMP3 in mice and identified the protein as a new endogenous signaling molecule that shapes diverse features of the hippocampal pyramidal dendrites without affecting axon morphology. We also found that CRMP3 protects dendrites against dystrophy induced by prion peptide PrP(106-126). Here, we report that CRMP3 has a profound influence on neurite initiation and dendrite growth of hippocampal neurons in vitro. Our deletional mapping revealed that the C-terminus of CRMP3 probably harbors its dendritogenic capacity and supports an active transport mechanism. By contrast, overexpression of the C-terminal truncated CRMP3 phenocopied the effect of CRMP3 gene deletion with inhibition of neurite initiation or decrease in dendrite complexity, depending on the stage of cell development. In addition, this mutant inhibited the activity of CRMP3, in a similar manner to siRNA. Voltage-gated calcium channel inhibitors prevented CRMP3-induced dendritic growth and somatic Ca(2+) influx in CRMP3-overexpressing neurons was augmented largely via L-type channels. These results support a link between CRMP3-mediated Ca(2+) influx and CRMP3-mediated dendritic growth in hippocampal neurons.
authors.affiliation: Lyon Neuroscience Research Center INSERM U1028/CNRS UMR 5292, F-69372 Lyon, France.
authors.forename: Tam T
authors.initials: TT
authors.lastname: Quach
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Wilson
authors.forename: Veronique
authors.initials: V
authors.lastname: Rogemond
authors.forename: Naura
authors.initials: N
authors.lastname: Chounlamountri
authors.forename: Pappachan E
authors.initials: PE
authors.lastname: Kolattukudy
authors.forename: Stephanie
authors.initials: S
authors.lastname: Martinez
authors.forename: May
authors.initials: M
authors.lastname: Khanna
authors.forename: Marie-Francoise
authors.initials: MF
authors.lastname: Belin
authors.forename: Rajesh
authors.initials: R
authors.lastname: Khanna
authors.forename: Jerome
authors.initials: J
authors.lastname: Honnorat
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Duchemin
mesh_terms: D000818:Animals; D015220:Calcium Channels / Q000378:metabolism* / Q000502:physiology; D003712:Dendrites / Q000378:metabolism* / Q000502:physiology; D006624:Hippocampus / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D009024:Morphogenesis; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection
chemical_list: D015220:Calcium Channels; C405926:Dpysl4 protein, mouse; D009419:Nerve Tissue Proteins
keywords: CRMP3; Ca2+ flux; Dendrite morphogenesis; Hippocampal neurons; Lamellipodia; Neurite initiation