TY - JOUR

T1 - Diverse roles of extracellular calcium-sensing receptor in the central nervous system

AU - Bandyopadhyay, Sanghamitra

AU - Tfelt-Hansen, Jacob

AU - Chattopadhyay, Naibedya

PY - 2010/8/1

Y1 - 2010/8/1

N2 - The G-protein-coupled calcium-sensing receptor (CaSR), upon activation by Ca2+ or other physiologically relevant polycationic molecules, performs diverse functions in the brain. The CaSR is widely expressed in the central nervous system (CNS) and is characterized by a robust increase in its expression during postnatal brain development over adult levels throughout the CNS. Developmental increases in CaSR levels in brain correlate with myelinogenesis. Indeed, neural stem cells differentiating to the oligodendrocyte lineage exhibit the highest CaSR expression compared with those differentiating to astrocytic or neuronal lineages. In adult CNS, CaSR has broad relevance in maintaining local ionic homeostasis. CaSR shares an evolutionary relationship with the metabotropic glutamate receptor and forms heteromeric complexes with the type B-aminobutyric acid receptor subunits that affects its cell surface expression, activation, signaling, and functions. In normal physiology as well as in pathologic conditions, CaSR is activated by signals arising from mineral ions, amino acids, polyamines, glutathione, and amyloid-β in conjunction with Ca2+1 and other divalent cationic ligands. CaSR activation regulates membrane excitability of neurons and glia and affects myelination, olfactory and gustatory signal integration, axonal and dendritic growth, and gonadotrophin-releasing hormonalneuronal migration. Insofar as the CaSR is a clinically important therapeutic target for parathyroid disorders, development of its agonists or antagonists as therapeutics for CNS disorder could be a major breakthrough.

AB - The G-protein-coupled calcium-sensing receptor (CaSR), upon activation by Ca2+ or other physiologically relevant polycationic molecules, performs diverse functions in the brain. The CaSR is widely expressed in the central nervous system (CNS) and is characterized by a robust increase in its expression during postnatal brain development over adult levels throughout the CNS. Developmental increases in CaSR levels in brain correlate with myelinogenesis. Indeed, neural stem cells differentiating to the oligodendrocyte lineage exhibit the highest CaSR expression compared with those differentiating to astrocytic or neuronal lineages. In adult CNS, CaSR has broad relevance in maintaining local ionic homeostasis. CaSR shares an evolutionary relationship with the metabotropic glutamate receptor and forms heteromeric complexes with the type B-aminobutyric acid receptor subunits that affects its cell surface expression, activation, signaling, and functions. In normal physiology as well as in pathologic conditions, CaSR is activated by signals arising from mineral ions, amino acids, polyamines, glutathione, and amyloid-β in conjunction with Ca2+1 and other divalent cationic ligands. CaSR activation regulates membrane excitability of neurons and glia and affects myelination, olfactory and gustatory signal integration, axonal and dendritic growth, and gonadotrophin-releasing hormonalneuronal migration. Insofar as the CaSR is a clinically important therapeutic target for parathyroid disorders, development of its agonists or antagonists as therapeutics for CNS disorder could be a major breakthrough.

KW - Development

KW - G-protein-coupled receptor

KW - Glioma

KW - Membrane polarization

KW - Oligodendrogenesis

UR - http://www.scopus.com/inward/record.url?scp=77953629714&partnerID=8YFLogxK

U2 - 10.1002/jnr.22391

DO - 10.1002/jnr.22391

M3 - Review

C2 - 20336672

AN - SCOPUS:77953629714

VL - 88

SP - 2073

EP - 2082

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 10

ER -