CRP1, a protein localized in filopodia of growth cones, is involved in dendritic growth.
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CRP1, a protein localized in filopodia of growth cones, is involved in dendritic growth. / Ma, Liping; Greenwood, Jeffrey A; Schachner, Melitta.
In: J NEUROSCI, Vol. 31, No. 46, 46, 2011, p. 16781-16791.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - CRP1, a protein localized in filopodia of growth cones, is involved in dendritic growth.
AU - Ma, Liping
AU - Greenwood, Jeffrey A
AU - Schachner, Melitta
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Animals
KW - Male
KW - Female
KW - Cells, Cultured
KW - Up-Regulation
KW - Cercopithecus aethiops
KW - Rats
KW - Analysis of Variance
KW - Microscopy, Confocal
KW - Embryo, Mammalian
KW - Hippocampus/cytology
KW - Calcium/metabolism
KW - RNA, Messenger/metabolism
KW - RNA, Small Interfering/genetics/metabolism
KW - Actins/metabolism
KW - Dendrites/physiology
KW - Enzyme Inhibitors/pharmacology
KW - Calcium Channel Blockers/pharmacology
KW - Transfection/methods
KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/pharmacology
KW - CREB-Binding Protein/metabolism
KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
KW - Chelating Agents/pharmacology
KW - Cystatins/genetics/metabolism
KW - Egtazic Acid/pharmacology
KW - Green Fluorescent Proteins/genetics
KW - Growth Cones/metabolism/ultrastructure
KW - Neurites/metabolism/ultrastructure
KW - Neurons/cytology/drug effects
KW - Nifedipine/pharmacology
KW - Potassium Chloride/pharmacology
KW - Pseudopodia/metabolism
KW - Valine/analogs & derivatives/pharmacology
KW - Animals
KW - Male
KW - Female
KW - Cells, Cultured
KW - Up-Regulation
KW - Cercopithecus aethiops
KW - Rats
KW - Analysis of Variance
KW - Microscopy, Confocal
KW - Embryo, Mammalian
KW - Hippocampus/cytology
KW - Calcium/metabolism
KW - RNA, Messenger/metabolism
KW - RNA, Small Interfering/genetics/metabolism
KW - Actins/metabolism
KW - Dendrites/physiology
KW - Enzyme Inhibitors/pharmacology
KW - Calcium Channel Blockers/pharmacology
KW - Transfection/methods
KW - 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives/pharmacology
KW - CREB-Binding Protein/metabolism
KW - Calcium-Calmodulin-Dependent Protein Kinase Type 2/metabolism
KW - Chelating Agents/pharmacology
KW - Cystatins/genetics/metabolism
KW - Egtazic Acid/pharmacology
KW - Green Fluorescent Proteins/genetics
KW - Growth Cones/metabolism/ultrastructure
KW - Neurites/metabolism/ultrastructure
KW - Neurons/cytology/drug effects
KW - Nifedipine/pharmacology
KW - Potassium Chloride/pharmacology
KW - Pseudopodia/metabolism
KW - Valine/analogs & derivatives/pharmacology
M3 - SCORING: Journal article
VL - 31
SP - 16781
EP - 16791
JO - J NEUROSCI
JF - J NEUROSCI
SN - 0270-6474
IS - 46
M1 - 46
ER -