Regulation of neurite growth by spontaneous Ca2+ oscillations in astrocytes.
Astrocytes play a pivotal role in the regulation of neurite growth, but the intracellular signaling mechanism in astrocytes that mediates this regulation remains unclarified. We studied the relationship between spontaneous Ca(2+) oscillations in astrocytes and the astrocyte-mediated neurite growth. We generated Ca(2+) signal-deficient astrocytes in which spontaneous Ca(2+) oscillations were abolished by a chronic inhibition of IP(3) signaling. When hippocampal neurons were cultured on a monolayer of Ca(2+) signal-deficient astrocytes, the growth of dendrites and axons was inhibited. Time-lapse imaging of the advancement of axonal growth cones indicated the involvement of membrane-bound molecules for this inhibition. Among six candidate membrane-bound molecules that may modulate neuronal growth, N-cadherin was downregulated in Ca(2+) signal-deficient astrocytes. Although a blocking antibody to N-cadherin suppressed the axonal growth on control astrocytes, extrinsic N-cadherin expression rescued the suppressed axonal growth on Ca(2+) signal-deficient astrocytes. These findings suggest that spontaneous Ca(2+) oscillations regulate the astrocytic function to promote neurite growth by maintaining the expression of specific growth-enhancing proteins on their surface, and that N-cadherin is one of such molecules.
Kanemaru
Kazunori
K
Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Okubo
Yohei
Y
Hirose
Kenzo
K
Iino
Masamitsu
M
D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D004347:Drug Interactions; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology; D006624:Hippocampus / Q000166:cytology; D000072181:Inositol Polyphosphate 5-Phosphatases; D009154:Mutation / Q000502:physiology; D016501:Neurites / Q000502:physiology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019284:Thapsigargin / Q000494:pharmacology; D014162:Transfection / Q000379:methods; D014404:Tubulin / Q000378:metabolism
D004791:Enzyme Inhibitors; D005904:Glial Fibrillary Acidic Protein; C488416:Tubb3 protein, rat; D014404:Tubulin; D019284:Thapsigargin; D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D002118:Calcium
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