title: Critical role of collapsin response mediator protein-associated molecule CRAM for filopodia and growth cone development in neurons.
abstract: Collapsin response mediator proteins (CRMPs) have been implicated in signaling of axonal guidance, including semaphorins. We have previously identified a unique member of this gene family, CRMP-associated molecule CRAM (CRMP-5), which is phylogenetically divergent from the other four CRMPs. In this study, we have examined the distribution and function of CRAM in developing neurons. Immunohistochemical analysis showed accumulation of CRAM in the filopodia of growth cones. Experiments using cytochalasin D indicated that filopodial localization of CRAM was independent of filamentous actin. Overexpression of CRAM in neuronal cells significantly promoted filopodial growth and led to the formation of supernumerary growth cones, which acquired resistance to semaphorin-3A stimulation. Finally, knockdown of CRAM by using RNA interference blocked filopodial formation and revealed an aberrant morphology of growth cones. We propose that CRAM regulates filopodial dynamics and growth cone development, thereby restricting the response of growth cone to repulsive guidance cues.
authors.affiliation: Division of Proteomics, Department of Genome Sciences, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
authors.forename: Azusa
authors.initials: A
authors.lastname: Hotta
authors.forename: Ryoko
authors.initials: R
authors.lastname: Inatome
authors.forename: Junichi
authors.initials: J
authors.lastname: Yuasa-Kawada
authors.forename: Qingyu
authors.initials: Q
authors.lastname: Qin
authors.forename: Hirohei
authors.initials: H
authors.lastname: Yamamura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Yanagi
mesh_terms: D000199:Actins / Q000378:metabolism; D000581:Amidohydrolases / Q000235:genetics* / Q000502:physiology*; D000818:Animals; D019556:COS Cells; D049109:Cell Proliferation; D015638:Cytochalasin D / Q000494:pharmacology; D005786:Gene Expression Regulation; D006624:Hippocampus / Q000378:metabolism; D006867:Hydrolases; D015151:Immunoblotting; D007150:Immunohistochemistry; D051379:Mice; D008856:Microscopy, Fluorescence; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D040121:Semaphorin-3A / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D000199:Actins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D034741:RNA, Small Interfering; D040121:Semaphorin-3A; D015638:Cytochalasin D; C415087:DPYSL5 protein, human; C501733:Dpysl5 protein, mouse; D006867:Hydrolases; D000581:Amidohydrolases