| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA
The spatial distribution of Ca2+ signalling molecules is critical for establishing specific interactions that control Ca2+ signal generation and transduction. In many cells, close physical coupling of Ca2+ channels and their targets enables precise and robust activation of effector molecules through local [Ca2+]i elevation in microdomains. In T cells, the plasma membrane Ca2+-ATPase (PMCA) is a major target of Ca2+ influx through Ca2+ release-activated Ca2+ (CRAC) channels. Elevation of [Ca2+]i slowly modulates pump activity to ensure the stability and enhance the dynamic nature of Ca2+ signals. In this study we probed the functional organization of PMCA and CRAC channels in T cells by manipulating Ca2+ microdomains near CRAC channels and measuring the resultant modulation of PMCAs. The amplitude and spatial extent of microdomains was increased by elevating the rate of Ca2+ entry, either by raising extracellular [Ca2+], by increasing the activity of CRAC channels with 2-aminoethoxyborane (2-APB), or by hyperpolarizing the plasma membrane. Surprisingly, doubling the rate of Ca2+ influx does not further increase global [Ca2+]i in a substantial fraction of cells, due to a compensatory increase in PMCA activity. The enhancement of PMCA activity without changes in global [Ca2+]i suggests that local [Ca2+]i microdomains near CRAC channels effectively promote PMCA modulation. These results reveal an intimate functional association between CRAC channels and Ca2+ pumps in the plasma membrane which may play an important role in governing the time course and magnitude of Ca2+ signals in T cells.
(Received 17 December 2003;
accepted after revision 12 February 2004;
first published online 13 February 2004)
Corresponding author R. S. Lewis: Beckman Center B-111A, Stanford University School of Medicine, Stanford, CA 94305, USA. Email: rslewis{at}stanford.edu
This article has been cited by other articles:
|
|
 |
|
  A. B. Parekh Ca2+ microdomains near plasma membrane Ca2+ channels: impact on cell function J. Physiol., July 1, 2008; 586(13): 3043 - 3054. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 W.-C. Chang, J. Di Capite, K. Singaravelu, C. Nelson, V. Halse, and A. B. Parekh Local Ca2+ Influx through Ca2+ Release-activated Ca2+ (CRAC) Channels Stimulates Production of an Intracellular Messenger and an Intercellular Pro-inflammatory Signal J. Biol. Chem., February 22, 2008; 283(8): 4622 - 4631. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. B. Montalvo, A. R. Artalejo, and J. A. Gilabert ATP from Subplasmalemmal Mitochondria Controls Ca2+-dependent Inactivation of CRAC Channels J. Biol. Chem., November 24, 2006; 281(47): 35616 - 35623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Won and D. I. Yule Measurement of Ca2+ signaling dynamics in exocrine cells with total internal reflection microscopy Am J Physiol Gastrointest Liver Physiol, July 1, 2006; 291(1): G146 - G155. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Spassova, J. Soboloff, L.-P. He, W. Xu, M. A. Dziadek, and D. L. Gill STIM1 has a plasma membrane role in the activation of store-operated Ca2+ channels. PNAS, March 14, 2006; 103(11): 4040 - 4045. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. K. Neumann, J. Yang, M. P. Biju, S. K. Joseph, R. S. Johnson, V. H. Haase, B. D. Freedman, and L. A. Turka Hypoxia inducible factor 1{alpha} regulates T cell receptor signal transduction PNAS, November 22, 2005; 102(47): 17071 - 17076. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Feske, M. Prakriya, A. Rao, and R. S. Lewis A severe defect in CRAC Ca2+ channel activation and altered K+ channel gating in T cells from immunodeficient patients J. Exp. Med., September 6, 2005; 202(5): 651 - 662. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
V. A. Golovina Visualization of localized store-operated calcium entry in mouse astrocytes. Close proximity to the endoplasmic reticulum J. Physiol., May 1, 2005; 564(3): 737 - 749. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. B. Parekh and J. W. Putney Jr. Store-Operated Calcium Channels Physiol Rev, April 1, 2005; 85(2): 757 - 810. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Aneiros, S. Philipp, A. Lis, M. Freichel, and A. Cavalie Modulation of Ca2+ Signaling by Na+/Ca2+ Exchangers in Mast Cells J. Immunol., January 1, 2005; 174(1): 119 - 130. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
