期刊
JOURNAL OF NEUROSCIENCE
卷 35, 期 4, 页码 1739-1752出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1714-14.2015
关键词
calcium; cell adhesion molecule; neurite outgrowth; neurons; voltage-dependent Ca2+ channel
资金
- National Health and Medical Research Council
- Rebecca L. Cooper Medical Research Foundation
Changes in expression of the neural cell adhesion molecule 2 (NCAM2) have been proposed to contribute to neurodevelopmental disorders in humans. The role of NCAM2 in neuronal differentiation remains, however, poorly understood. Using genetically encoded Ca2+ reporters, we show that clustering of NCAM2 at the cell surface of mouse cortical neurons induces submembrane [Ca2+] spikes, which depend on the L-type voltage-dependent Ca2+ channels (VDCCs) and require activation of the protein tyrosine kinase c-Src. We also demonstrate that clustering of NCAM2 induces L-type VDCC-and c-Src-dependent activation of CaMKII. NCAM2-dependent submembrane [Ca2+] spikes colocalize with the bases of filopodia. NCAM2 activation increases the density of filopodia along neurites and neurite branching and outgrowth in an L-type VDCC-, c-Src-, and CaMKII-dependent manner. Our results therefore indicate thatNCAM2 promotes the formation of filopodia and neurite branching by inducing Ca2+ influx and CaMKII activation. Changes in NCAM2 expression in Down syndrome and autistic patients may therefore contribute to abnormal neurite branching observed in these disorders.
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