Printer Friendly

Caveolar microdomains as organizers of calcium signaling.

[Ca.sup.2+] is a major signaling molecule in both excitable and non-excitable cells, where it modulates a variety of cellular functions ranging from cell growth to differentiation to cell death. Across a wide spatial and temporal range, several [Ca.sup.2+] channels generate [Ca.sup.2+] signals that can last from microseconds to minutes. This broad range of [Ca.sup.2+] signals can be efficiently coordinated through organization of specific [Ca.sup.2+] channels, pumps, buffers, exchangers and protein scaffolds at common microdomains. Lipid rafts/ caveolae serve as such a plasma membrane (PM) microdomain wherein highly specific signaling molecules are assembled so as to efficiently execute a defined signaling event with precision. Unlike the membrane rafts, which are planar, 'Caveolae'--a raft subset represent flask/omega shaped membrane invaginations that ate widely expressed in a variety of cell types. Caveolae are cholesterol rich specialized PM domains with Caveolin1 (Cav1) as their major structural protein. These membrane domains represent a major cellular sub-compartment that facilitates various signal transduction events including [Ca.sup.2+] influx. Transient receptor potential canonical-1 (TRPC1) constitute an integral component of PM [Ca.sup.2+] channels that initiates store operated [Ca.sup.2+] entry (SOCE) following the depletion of endoplasmic reticulum (ER) [Ca.sup.2+]. One of the important questions regarding SOCE that has been actively pursued is about the molecular mechanism(s) whereby the status of the ER [Ca.sup.2+] store is communicated to the plasma membrane channels to initiate [Ca.sup.2+] influx. Recent, studies from several laboratories have identified the involvement of stromal interaction molecule-1(STIM1) in this process. STIM1 is expressed in the ER as a single transmembrane protein which can sense the changes in ER [Ca.sup.2+] levels. Following depletion of ER [Ca.sup.2+], STIM1 forms clusters at the ER-PM junctional regions, where it physically associates with PM channels and activates SOCE. Here we demonstrate the association of TRPC1 and STIM1 with caveolar compartments of the PM. Depletion of ER [Ca.sup.2+] stores enhanced the recruitment of TRPC1 protein to plasma membrane rafts and its interaction with STIM1. Disruption of caveolar domains by sequestering membrane cholesterol altered raft-associated TRPC1 localization, its interaction with STIM1 and eventually SOCE. Additionally, silencing of Cav1 severely reduced the PM association of TRPC1 and in cav1 knockout tissues; membrane raft association of TRPC1 was abolished. Altogether, our findings demonstrate activation of TRPC1 relies on its association with STIM1 and on the integrity of caveolar micro-domains. In conclusion, we propose that the association of TRPC1 with Cav1 is required for targeting the channel to specific PM compartments, where it functionally associates with its activator STIM1, thereby, providing a substantial evidence for caveolae as organizers of TRPC1 mediated [Ca.sup.2+] signaling.

Funding:

We duly acknowledge grant support from the NSF (0548733) and the NIH (DE017102, 5P20RR017699) awarded to B.B.S anda ND-EPSCoR fellowship award to B.P.

Biswaranjan Pani, Hweiling Ong *, Xibao Liu *, Kristina Rauser, Virginia Achen, Indu Ambudkar * and Brij B Singh

Department of Biochemistry and Molecular Biology, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58201, * NIDCR, NIH, Bethesda, MD 20892
COPYRIGHT 2009 North Dakota Academy of Science
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2009 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Title Annotation:COMMUNICATIONS--GRADUATE
Author:Pani, Biswaranjan; Ong, Hweiling; Liu, Xibao; Rauser, Kristina; Achen, Virginia; Ambudkar, Indu; Sin
Publication:Proceedings of the North Dakota Academy of Science
Article Type:Abstract
Geographic Code:1USA
Date:Apr 1, 2009
Words:524
Previous Article:A new interpretation of the paleoecology of the big pig dig quarry, Badlands National Park, South Dakota.
Next Article:Increasing the sensitivity of advanced stage of prostate cancer to chemotherapeutic drugs-induced apoptosis by targeting miR-205 and miR-31.
Topics:

Terms of use | Privacy policy | Copyright © 2021 Farlex, Inc. | Feedback | For webmasters