The Journal of Neuroscience, August 15, 2007, 27(33):8957-8966; doi:10.1523/JNEUROSCI.2276-07.2007
Previous Article | Next Article 
Cellular/Molecular
Regulation of Neurite Growth by Spontaneous Ca2+ Oscillations in Astrocytes
Kazunori Kanemaru,1
Yohei Okubo,1
Kenzo Hirose,2 and
Masamitsu Iino1
1Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan, and 2Department of Cell Physiology, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan
Correspondence should be addressed to Masamitsu Iino at the above address. Email: iino{at}m.u-tokyo.ac.jp
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 Ca2+ oscillations in astrocytes and the astrocyte-mediated neurite growth. We generated Ca2+ signal-deficient astrocytes in which spontaneous Ca2+ oscillations were abolished by a chronic inhibition of IP3 signaling. When hippocampal neurons were cultured on a monolayer of Ca2+ 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 Ca2+ 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 Ca2+ signal-deficient astrocytes. These findings suggest that spontaneous Ca2+ 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.
Key words: spontaneous calcium oscillation; neuron-glia interaction; neurite growth; inositol 1,4,5-trisphosphate; astrocyte; N-cadherin
Received May 18, 2007;
revised June 25, 2007;
accepted July 8, 2007.
Correspondence should be addressed to Masamitsu Iino at the above address. Email: iino{at}m.u-tokyo.ac.jp
Related articles in J. Neurosci.:
- This Week in The Journal
J. Neurosci. 2007 27: i.
[Full Text]