14-3-3 Proteins Buffer Intracellular Calcium Sensing Receptors to Constrain Signaling

PloS One
Michael P GrantGerda E Breitwieser

Abstract

Calcium sensing receptors (CaSR) interact with 14-3-3 binding proteins at a carboxyl terminal arginine-rich motif. Mutations identified in patients with familial hypocalciuric hypercalcemia, autosomal dominant hypocalcemia, pancreatitis or idiopathic epilepsy support the functional importance of this motif. We combined total internal reflection fluorescence microscopy and biochemical approaches to determine the mechanism of 14-3-3 protein regulation of CaSR signaling. Loss of 14-3-3 binding caused increased basal CaSR signaling and plasma membrane levels, and a significantly larger signaling-evoked increase in plasma membrane receptors. Block of core glycosylation with tunicamycin demonstrated that changes in plasma membrane CaSR levels were due to differences in exocytic rate. Western blotting to quantify time-dependent changes in maturation of expressed wt CaSR and a 14-3-3 protein binding-defective mutant demonstrated that signaling increases synthesis to maintain constant levels of the immaturely and maturely glycosylated forms. CaSR thus operates by a feed-forward mechanism, whereby signaling not only induces anterograde trafficking of nascent receptors but also increases biosynthesis to maintain steady state levels of net...Continue Reading

References

Feb 7, 1998·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·P K GoldsmithA M Spiegel
Feb 13, 2001·Trends in Pharmacological Sciences·P TsaoM von Zastrow
May 15, 2001·American Journal of Physiology. Cell Physiology·G E Breitwieser, L Gama
Aug 11, 2001·Biochemical Society Transactions·M von Zastrow
Nov 10, 2001·The Journal of Clinical Endocrinology and Metabolism·A LienhardtM Garabédian
Jun 12, 2002·The Journal of Biological Chemistry·Ayça Akal-StraderJeffrey M Becker
Aug 31, 2004·The Journal of Pharmacology and Experimental Therapeutics·Lauren T MayArthur Christopoulos
Jan 20, 2005·The Journal of Biological Chemistry·Mingliang Zhang, Gerda E Breitwieser
Feb 9, 2005·Critical Reviews in Clinical Laboratory Sciences·Jacob Tfelt-Hansen, Edward M Brown
Apr 23, 2005·Science·Robert J Lefkowitz, Sudha K Shenoy
Feb 25, 2006·Scandinavian Journal of Gastroenterology·P FelderbauerW E Schmidt
Aug 30, 2008·Chemistry & Biology·Alexey A Pakhomov, Vladimir I Martynov
Sep 22, 2009·The Journal of Pharmacology and Experimental Therapeutics·Rachel L ThomasR A John Challiss
Sep 26, 2009·Molecular Pharmacology·Zuzana SaidakRomuald Mentaverri
Apr 28, 2010·The Journal of Biological Chemistry·Alice CavanaughGerda E Breitwieser
Aug 24, 2010·Endocrine Reviews·Aaron L MagnoThomas Ratajczak
Aug 28, 2010·Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology·Ann StepanchickGerda E Breitwieser
Feb 18, 2011·Experimental Neurology·Laxmikant S DeshpandeRobert J DeLorenzo
Apr 5, 2011·Analytical Biochemistry·Ryo IizukaTakashi Funatsu
Aug 16, 2011·Advances in Bioscience and Biotechnology·Matthew J Mahon
Sep 29, 2011·Seminars in Cell & Developmental Biology·Alexandra K Gardino, Michael B Yaffe
Sep 29, 2011·European Journal of Pharmacology·María Ángeles RuizMairena Martín
Mar 29, 2012·Advances in Experimental Medicine and Biology·Bandana ChakravartiEdward M Brown
Jul 17, 2013·Best Practice & Research. Clinical Endocrinology & Metabolism·Gerda E Breitwieser
Jul 17, 2013·Best Practice & Research. Clinical Endocrinology & Metabolism·Arthur D Conigrave, Donald T Ward
Jul 17, 2013·Best Practice & Research. Clinical Endocrinology & Metabolism·Edward M Brown
Nov 15, 2013·American Journal of Physiology. Cell Physiology·Brandie M CrossRajini Rao
Feb 20, 2014·Frontiers in Genetics·Marina Uhart, Diego M Bustos
Jul 6, 2014·Frontiers in Molecular Neuroscience·Pilar Rivero-RíosSabine Hilfiker
Sep 23, 2014·Cell Calcium·Patrick GilonMagalie A Ravier

❮ Previous
Next ❯

Citations

Nov 1, 2016·Hormone Research in Pædiatrics·Diana-Alexandra ErtlGabriele Haeusler
Mar 17, 2021·Nature Communications·Gergo GoglNikolai N Sluchanko

❮ Previous
Next ❯

Methods Mentioned

BETA
transfection
Fluorescence
ELISA
glycosylation

Software Mentioned

FUJI Film Multi Gauge
GraphPad Prism
ImageJ
μManager

Related Concepts

Related Feeds

Calcium & Bioenergetics

Bioenergetic processes, including cellular respiration and photosynthesis, concern the transformation of energy by cells. Here is the latest research on the role of calcium in bioenergetics.

Related Papers

Cellular Physiology and Biochemistry : International Journal of Experimental Cellular Physiology, Biochemistry, and Pharmacology
Ann StepanchickGerda E Breitwieser
Nihon rinsho. Japanese journal of clinical medicine
S Okamoto
Internal Medicine
Katsuhiko Yonemura, Akira Hishida
© 2021 Meta ULC. All rights reserved