Regulation of axonal and dendritic growth by the extracellular calcium-sensing receptor.
The extracellular calcium-sensing receptor (CaSR) monitors the systemic, extracellular, free ionized-calcium level ([Ca(2+)](o)) in organs involved in systemic [Ca(2+)](o) 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 [Ca(2+)](o), 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.
Vizard
Thomas N
TN
School of Biosciences, Biomedical Building, Museum Avenue, Cardiff, CF10 3US, UK.
O'Keeffe
Gerard W
GW
Gutierrez
Humberto
H
Kos
Claudine H
CH
Riccardi
Daniela
D
Davies
Alun M
AM
D000818:Animals; D001369:Axons / Q000378:metabolism* / Q000648:ultrastructure; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics*; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics; D048430:Cell Shape / Q000235:genetics; D002478:Cells, Cultured; D003712:Dendrites / Q000378:metabolism* / Q000648:ultrastructure; D005456:Fluorescent Dyes; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000196:embryology* / Q000254:growth & development*; D020439:Growth Cones / Q000378:metabolism / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D008164:Luminescent Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016501:Neurites / Q000378:metabolism / Q000648:ultrastructure; D009924:Organ Culture Techniques; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D044169:Receptors, Calcium-Sensing / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*
D005456:Fluorescent Dyes; D008164:Luminescent Proteins; D044169:Receptors, Calcium-Sensing