Dual regulation of LIM kinase 1 expression by cyclic AMP and calcium determines cofilin phosphorylation states during neuritogenesis in NG108-15 cells.
The present study was designed to elucidate the cellular and molecular mechanisms of neuritogenesis in differentiating neurons. For this purpose, we used pharmacological and immunochemical techniques to determine the intracellular signal transduction pathways that regulate actin dynamics during neuritogenesis. We confirmed that a rise in intracellular cyclic AMP (cAMP) concentration stimulated cells to increase their neurite numbers, and that this increase of neurites was suppressed by activation of calcineurin induced by a Ca2+ influx through voltage-dependent Ca2+ channels. Expression of a specific cofilin kinase (LIM kinase 1) was increased and decreased by cAMP and Ca2+ cascades, respectively. The phosphorylation state, but not the level of expression, of a potent regulator of actin dynamics (cofilin) was strongly correlated with the expression level of LIM kinase 1. Our results suggest that polymerization and depolymerization of actin by cofilin phosphorylation is necessary for neuritogenesis in differentiating neurons.
Tojima
Takuro
T
Division of Biological Sciences, Graduate School of Science, Hokkaido University, North 10, West 8, Kita-ku, Sapporo 060-0810, Japan.
Takahashi
Masayuki
M
Ito
Etsuro
E
D051339:Actin Depolymerizing Factors; D000199:Actins / Q000378:metabolism; D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D000242:Cyclic AMP / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D005910:Glioma / Q000378:metabolism; D006822:Hybrid Cells / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D054461:Lim Kinases; D051379:Mice; D008840:Microfilament Proteins / Q000737:chemistry / Q000378:metabolism*; D009447:Neuroblastoma / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000096:biosynthesis*; D051381:Rats; D015398:Signal Transduction / Q000502:physiology*; D014407:Tumor Cells, Cultured
D051339:Actin Depolymerizing Factors; D000199:Actins; D008840:Microfilament Proteins; D000242:Cyclic AMP; D011494:Protein Kinases; D054461:Lim Kinases; C515893:Limk1 protein, mouse; C515894:Limk1 protein, rat; D019703:Calcineurin; D002118:Calcium