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Contribution of Ca 2+ calmodulin‐dependent protein kinase II and mitogen‐activated protein kinase kinase to neural activity‐induced neurite outgrowth and survival of cerebellar granule cells
Author(s) -
Borodinsky Laura N.,
Coso Omar A.,
Fiszman Mónica L.
Publication year - 2002
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2002.00795.x
Subject(s) - microbiology and biotechnology , neurite , protein kinase a , biology , kinase , cyclin dependent kinase 5 , calmodulin , mitogen activated protein kinase kinase , cerebellum , cyclin dependent kinase 2 , map2k7 , chemistry , biochemistry , neuroscience , in vitro , enzyme
In this report we describe our studies on intracellular signals that mediate neurite outgrowth and long‐term survival of cerebellar granule cells. The effect of voltage‐gated calcium channel activation on neurite complexity was evaluated in cultured cerebellar granule cells grown for 48 h at low density; the parameter measured was the fractal dimension of the cell. We explored the contribution of two intracellular pathways, Ca 2+ calmodulin‐dependent protein kinase II and mitogen‐activated protein kinase kinase (MEK1), to the effects of high [K + ] e under serum‐free conditions. We found that 25 m m KCl (25K) induced an increase in calcium influx through L subtype channels. In neurones grown for 24–48 h under low‐density conditions, the activation of these channels induced neurite outgrowth through the activation of Ca 2+ calmodulin‐dependent protein kinase II. This also produced an increase in long‐term neuronal survival with a partial contribution from the MEK1 pathway. We also found that the addition of 25K increased the levels of the phosphorylated forms of Ca 2+ calmodulin‐dependent protein kinase II and of the extracellular signal‐regulated kinases 1 and 2. Neuronal survival under resting conditions is supported by the MEK1 pathway. We conclude that intracellular calcium oscillations can triggered different biological effects depending on the stage of maturation of the neuronal phenotype. Ca 2+ calmodulin‐dependent protein kinase II activation determines the growth of neurites and the development of neuronal complexity.