Calcium-induced synergistic inhibition of a translational factor eEF2 in nerve growth cones.
Local protein synthesis in nerve growth cones has been suggested, but how it is controlled remains largely unknown. We found eukaryotic elongation factor-2 (eEF2), a key component of mRNA translation, in growth cones by immunocytochemistry. While phosphorylated eEF2 was weakly distributed in advancing growth cones, eEF2 phosphorylation was increased by high potassium-evoked calcium influx. In the growth cone, calcium elevation increased eEF2 kinase (EF2K), a calcim-calmodulin-dependent enzyme. Calcium also decreased the level of phosphorylated p70-S6 kinase (S6K), a kinase known to inhibit EF2K. Moreover, calcium elevation decreased total eEF2 in growth cones. Since phosphorylated eEF2 inhibits mRNA translation, calcium elevation appears to inhibit mRNA translation in growth cones by a synergistic mechanism involving regulation of EF2K, S6K, and eEF2 itself. Time-lapse imaging showed that calcium elevation induced growth arrest of neurites. The inhibitory effect on mRNA translation may thus be involved in the regulation of neurite outgrowth.
Iizuka
Akira
A
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Fuku-ura 3-9, Kanazawa Ward, Yokohama 236-0004, Japan.
Sengoku
Kumiko
K
Iketani
Masumi
M
Nakamura
Fumio
F
Sato
Yasufumi
Y
Matsushita
Masayuki
M
Nairn
Angus C
AC
Takamatsu
Ken
K
Goshima
Yoshio
Y
Takei
Kohtaro
K
D000818:Animals; D002118:Calcium / Q000008:administration & dosage*; D049108:Cell Enlargement / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D015852:Eukaryotic Initiation Factor-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D005727:Ganglia, Spinal / Q000187:drug effects / Q000502:physiology*; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D014176:Protein Biosynthesis / Q000187:drug effects / Q000502:physiology*
D015852:Eukaryotic Initiation Factor-2; D002118:Calcium