title: Neural cell adhesion molecule 2 promotes the formation of filopodia and neurite branching by inducing submembrane increases in Ca2+ levels.
abstract: 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 Ca(2+) reporters, we show that clustering of NCAM2 at the cell surface of mouse cortical neurons induces submembrane [Ca(2+)] spikes, which depend on the L-type voltage-dependent Ca(2+) 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 [Ca(2+)] 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 that NCAM2 promotes the formation of filopodia and neurite branching by inducing Ca(2+) 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.
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, 2052 New South Wales, Australia.
authors: Lifu
authors: L
authors: Sheng
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, 2052 New South Wales, Australia.
authors: Iryna
authors: I
authors: Leshchyns'ka
authors: School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, 2052 New South Wales, Australia v.sytnyk@unsw.edu.au.
authors: Vladimir
authors: http://orcid.org/0000-0003-1927-2199
authors: V
authors: Sytnyk
mesh_terms: D000200:Action Potentials / Q000235:genetics; D033942:Adaptor Proteins, Vesicular Transport / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D002540:Cerebral Cortex / Q000166:cytology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019006:Neural Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000166:cytology*; D011189:Potassium Chloride / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011554:Pseudopodia / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D011743:Pyrimidines / Q000494:pharmacology
chemical_list: C412373:AG 1879; D033942:Adaptor Proteins, Vesicular Transport; D020746:Calcium Channels, L-Type; D004791:Enzyme Inhibitors; C480489:Lck-interacting protein, mouse; C108768:Ncam2 protein, mouse; D019006:Neural Cell Adhesion Molecules; D011743:Pyrimidines; D011189:Potassium Chloride; D011505:Protein-Tyrosine Kinases; D002118:Calcium
keywords: calcium; cell adhesion molecule; neurite outgrowth; neurons; voltage-dependent Ca2+ channel
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