INVESTIGADORES
REY Osvaldo
artículos
Título:
Requirement of the TRPC1 cation channel in the generation of transient Ca2+ oscillations by the calcium-sensing receptor.
Autor/es:
REY O, YOUNG SH, PAPAZYAN R, SHAPIRO MS, ROZENGURT E.
Revista:
JOURNAL OF BIOLOGICAL CHEMISTRY
Editorial:
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Referencias:
Año: 2006 p. 38730 - 38737
ISSN:
0021-9258
Resumen:
The calcium-sensing receptor (CaR) is an allosteric protein that
responds to extracellular Ca(2+) ([Ca(2+)](o)) and aromatic amino acids
with the production of different patterns of oscillations in
intracellular Ca(2+) concentration ([Ca(2+)](i)). An increase in
[Ca(2+)](o) stimulates phospholipase C-mediated production of inositol
1,4,5-trisphosphate and causes sinusoidal oscillations in [Ca(2+)](i).
Conversely, aromatic amino acid-induced CaR activation does not
stimulate phospholipase C but engages an unidentified signaling
mechanism that promotes transient oscillations in [Ca(2+)](i). We show
here that the [Ca(2+)](i) oscillations stimulated by aromatic amino
acids were selectively abolished by TRPC1 down-regulation using either
a pool of small inhibitory RNAs (siRNAs) or two different individual
siRNAs that targeted different coding regions of TRPC1. Furthermore,
[Ca(2+)](i) oscillations stimulated by aromatic amino acids were also
abolished by inhibition of TRPC1 function with an antibody that binds
the pore region of the channel. We also show that aromatic amino
acid-stimulated [Ca(2+)](i) oscillations can be prevented by protein
kinase C (PKC) inhibitors or siRNA-mediated PKCalpha down-regulation
and impaired by either calmodulin antagonists or by the expression of a
dominant-negative calmodulin mutant. We propose a model for the
generation of CaR-mediated transient [Ca(2+)](i) oscillations that
integrates its stimulation by aromatic amino acids with TRPC1
regulation by PKC and calmodulin.