title: CRP1, a protein localized in filopodia of growth cones, is involved in dendritic growth.
abstract: The cysteine-rich protein (CRP) family is a subgroup of LIM domain proteins. CRP1, which cross-links actin filaments to make actin bundles, is the only CRP family member expressed in the CNS with little known about its function in nerve cells. Here, we report that CRP1 colocalizes with actin in the filopodia of growth cones in cultured rat hippocampal neurons. Knockdown of CRP1 expression by short hairpin RNA interference results in inhibition of filopodia formation and dendritic growth in neurons. Overexpression of CRP1 increases filopodia formation and neurite branching, which require its actin-bundling activity. Expression of CRP1 with a constitutively active form of Cdc42, a GTPase involved in filopodia formation, increases filopodia formation in COS-7 cells, suggesting cooperation between the two proteins. Moreover, we demonstrate that neuronal activity upregulates CRP1 expression in hippocampal neurons via Ca²⁺ influx after depolarization. Ca²⁺/calmodulin-dependent protein kinase IV (CaMKIV) and cAMP response element binding protein mediate the Ca²⁺-induced upregulation of CRP1 expression. Furthermore, CRP1 is required for the dendritic growth induced by Ca²⁺ influx or CaMKIV. Together, these data are the first to demonstrate a role for CRP1 in dendritic growth.
authors.affiliation: W. M. Keck Center for Collaborative Neuroscience and Department of Cell Biology and Neuroscience, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA.
authors.forename: Liping
authors.initials: L
authors.lastname: Ma
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Greenwood
authors.forename: Melitta
authors.initials: M
authors.lastname: Schachner
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D050882:CREB-Binding Protein / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002478:Cells, Cultured; D002614:Chelating Agents / Q000494:pharmacology; D002522:Chlorocebus aethiops; D015891:Cystatins / Q000235:genetics / Q000378:metabolism*; D003712:Dendrites / Q000502:physiology*; D004533:Egtazic Acid / Q000494:pharmacology; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure*; D006624:Hippocampus / Q000166:cytology; D008297:Male; D018613:Microscopy, Confocal; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D011554:Pseudopodia / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014162:Transfection / Q000379:methods; D015854:Up-Regulation; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D000199:Actins; C079958:Andpro protein, rat; D002121:Calcium Channel Blockers; D002614:Chelating Agents; D015891:Cystatins; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D004533:Egtazic Acid; C063302:KN 62; D011189:Potassium Chloride; C056639:2-amino-5-phosphopentanoic acid; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D050882:CREB-Binding Protein; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D014633:Valine; D009543:Nifedipine; D002118:Calcium
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