Neuronal calcium sensor-1 modulation of optimal calcium level for neurite outgrowth.
Neurite extension and branching are affected by activity-dependent modulation of intracellular Ca2+, such that an optimal window of [Ca2+] is required for outgrowth. Our understanding of the molecular mechanisms regulating this optimal [Ca2+]i remains unclear. Taking advantage of the large growth cone size of cultured primary neurons from pond snail Lymnaea stagnalis combined with dsRNA knockdown, we show that neuronal calcium sensor-1 (NCS-1) regulates neurite extension and branching, and activity-dependent Ca2+ signals in growth cones. An NCS-1 C-terminal peptide enhances only neurite branching and moderately reduces the Ca2+ signal in growth cones compared with dsRNA knockdown. Our findings suggest that at least two separate structural domains in NCS-1 independently regulate Ca2+ influx and neurite outgrowth, with the C-terminus specifically affecting branching. We describe a model in which NCS-1 regulates cytosolic Ca2+ around the optimal window level to differentially control neurite extension and branching.
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, M5S 1A8, Canada.
Kwokyin
K
Hui
Guang-He
GH
Fei
Bechara J
BJ
Saab
Jiang
J
Su
John C
JC
Roder
Zhong-Ping
ZP
Feng
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D020013:Calcium Signaling; D017931:DNA Primers / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D008195:Lymnaea / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism*; D008958:Models, Molecular; D008959:Models, Neurological; D008969:Molecular Sequence Data; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D051580:Neuronal Calcium-Sensor Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics; D034622:RNA Interference; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D010446:Peptide Fragments; C101464:frequenin calcium sensor proteins; D012313:RNA