Regulation of axonal and dendritic growth by the extracellular calcium-sensing receptor

被引:95
作者
Vizard, Thomas N. [1 ]
O'Keeffe, Gerard W. [1 ]
Gutierrez, Humberto [1 ]
Kos, Claudine H. [2 ]
Riccardi, Daniela [1 ]
Davies, Alun M. [1 ]
机构
[1] Sch Biosci, Cardiff CF10 3US, S Glam, Wales
[2] Tufts Univ, Vitamins & Carcenogenesis Lab, HNRCA, Boston, MA 02111 USA
基金
英国生物技术与生命科学研究理事会; 英国惠康基金;
关键词
D O I
10.1038/nn2044
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
The extracellular calcium-sensing receptor (CaSR) monitors the systemic, extracellular, free ionized-calcium level ([Ca2(+)](0)) in organs involved in systemic [Ca2+](0) homeostasis. However, CaSR is also expressed in the nervous system, where its role is unknown. We found large amounts of CaSR in perinatal mouse sympathetic neurons when their axons were innervating and branching extensively in their targets. Manipulating CaSR function in these neurons by varying [Ca2+](0), using CaSR agonists and antagonists, or expressing a dominant-negative CaSR markedly affected neurite growth in vitro. Sympathetic neurons lacking CaSR had smaller neurite arbors in vitro, and sympathetic innervation density was reduced in CaSR-deficient mice in vivo. Hippocampal pyramidal neurons, which also express CaSR, had smaller dendrites when transfected with dominant-negative CaSR in postnatal organotypic cultures. Our findings reveal a crucial role for CaSR in regulating the growth of neural processes in the peripheral and central nervous systems.
引用
收藏
页码:285 / 291
页数:7
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