Regulation of neurite outgrowth mediated by neuronal calcium sensor-1 and inositol 1,4,5-trisphosphate receptor in nerve growth cones.
Calcium acts as an important second messenger in the intracellular signal pathways in a variety of cell functions. Strictly controlled intracellular calcium is required for proper neurite outgrowth of developing neurons. However, the molecular mechanisms of this process are still largely unknown. Neuronal calcium sensor-1 (NCS-1) is a high-affinity and low-capacity calcium binding protein, which is specifically expressed in the nervous system. NCS-1 was distributed throughout the entire region of growth cones located at a distal tip of neurite in cultured chick dorsal root ganglion neurons. In the central domain of the growth cone, however, NCS-1 was distributed in a clustered specific pattern and co-localized with the type 1 inositol 1,4,5-trisphosphate receptor (InsP(3)R1). The pharmacological inhibition of InsP(3) receptors decreased the clustered specific distribution of NCS-1 in the growth cones and inhibited neurite outgrowth but did not change the growth cone morphology. The acute and localized loss of NCS-1 function in the growth cone induced by chromophore-assisted laser inactivation (CALI) resulted in the growth arrest of neurites and lamellipodial and filopodial retractions. These findings suggest that NCS-1 is involved in the regulation of both neurite outgrowth and growth cone morphology. In addition, NCS-1 is functionally linked to InsP(3)R1, which may play an important role in the regulation of neurite outgrowth.
Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
M
M
Iketani
C
C
Imaizumi
F
F
Nakamura
A
A
Jeromin
K
K
Mikoshiba
Y
Y
Goshima
K
K
Takei
D000818:Animals; D001896:Boron Compounds / Q000008:administration & dosage; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000008:administration & dosage; D002478:Cells, Cultured; D002642:Chick Embryo; D005455:Fluorescent Antibody Technique; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D020439:Growth Cones / Q000187:drug effects / Q000502:physiology*; D015151:Immunoblotting; D007150:Immunohistochemistry; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D051580:Neuronal Calcium-Sensor Proteins / Q000378:metabolism*; D009479:Neuropeptides / Q000378:metabolism*; D011554:Pseudopodia / Q000502:physiology; D012433:Ryanodine / Q000008:administration & dosage; D019837:Ryanodine Receptor Calcium Release Channel / Q000378:metabolism; D013997:Time Factors
D001896:Boron Compounds; D002121:Calcium Channel Blockers; D053496:Inositol 1,4,5-Trisphosphate Receptors; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D019837:Ryanodine Receptor Calcium Release Channel; C101464:frequenin calcium sensor proteins; D012433:Ryanodine; C109986:2-aminoethoxydiphenyl borate; D002118:Calcium