TY - JOUR
T1 - Dual regulation of LIM kinase 1 expression by cyclic AMP and calcium determines cofilin phosphorylation states during neuritogenesis in NG108-15 cells
AU - Tojima, Takuro
AU - Takahashi, Masayuki
AU - Ito, Etsuro
N1 - Funding Information:
We are grateful to Dr. Takashi Obinata for providing antibody to cofilin and for his helpful comments on this manuscript. This work was partly supported by Research Fellowship (No. 10766) of the Japan Society for the Promotion of Science for Young Scientists to T.T., and by a Grant-in-Aid (No. 14540622) from the Japan Society for the Promotion of Science, a Grant-in-Aid (No. 13210006) from the Ministry of Education, Culture, Sports, Science and Technology of Japan and grants from the Inamori Foundation and the Brain Science Foundation to E.I.
PY - 2003/9/19
Y1 - 2003/9/19
N2 - 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.
AB - 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.
KW - Actin
KW - Calcineurin
KW - Neuronal differentiation
KW - Voltage-dependent Ca channel
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U2 - 10.1016/S0006-8993(03)03113-5
DO - 10.1016/S0006-8993(03)03113-5
M3 - Article
C2 - 12957367
AN - SCOPUS:0142058917
SN - 0006-8993
VL - 985
SP - 43
EP - 55
JO - Brain Research
JF - Brain Research
IS - 1
ER -