HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 38, 39374-39382, September 17, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/38/39374    most recent M405352200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gaertner, T. R. Articles by Waxham, M. N. Search for Related Content PubMed PubMed Citation Articles by Gaertner, T. R. Articles by Waxham, M. N. Social Bookmarking                      What's this?

RC3/Neurogranin and Ca²+/Calmodulin-dependent Protein Kinase II Produce Opposing Effects on the Affinity of Calmodulin for Calcium^*

Tara R. Gaertner, John A. Putkey¶, and M. Neal Waxham||

From the Departments of Neurobiology and Anatomy and ^¶Biochemistry and Molecular Biology, University of Texas Medical School, Houston, Texas 77030

The interaction of calmodulin with its target proteins is known to affect the kinetics and affinity of Ca²⁺ binding to calmodulin. Based on thermodynamic principles, proteins that bind to Ca²⁺-calmodulin should increase the affinity of calmodulin for Ca²⁺, while proteins that bind to apo-calmodulin should decrease its affinity for Ca²⁺. We quantified the effects on Ca²⁺-calmodulin interaction of two neuronal calmodulin targets: RC3, which binds both Ca²⁺- and apo-calmodulin, and CaM kinase II, which binds selectively to Ca²⁺-calmodulin. RC3 was found to decrease the affinity of calmodulin for Ca²⁺, whereas CaM kinase II increases the calmodulin affinity for Ca²⁺. Specifically, RC3 increases the rate of Ca²⁺ dissociation from the C-terminal sites of calmodulin up to 60-fold while having little effect on the rate of Ca²⁺ association. Conversely, CaM kinase II decreases the rates of dissociation of Ca²⁺ from both lobes of calmodulin and autophosphorylation of CaM kinase II at Thr²⁸⁶ induces a further decrease in the rates of Ca²⁺ dissociation. RC3 dampens the effects of CaM kinase II on Ca²⁺ dissociation by increasing the rate of dissociation from the C-terminal lobe of calmodulin when in the presence of CaM kinase II. This effect is not seen with phosphorylated CaM kinase II. The results are interpreted according to a kinetic scheme in which there are competing pathways for dissociation of the Ca²⁺-calmodulin target complex. This work indicates that the Ca²⁺ binding properties of calmodulin are highly regulated and reveals a role for RC3 in accelerating the dissociation of Ca²⁺-calmodulin target complexes at the end of a Ca²⁺ signal.

Received for publication, May 13, 2004 , and in revised form, June 23, 2004.

^* This work was supported by Grant NS26086 from the National Institutes of Health and Grant AU1144 from the Robert A. Welch Foundation. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Supported in part by a scholarship from the Natural Sciences and Engineering Research Council of Canada.

^|| To whom correspondence should be addressed: 6431 Fannin St., Houston, TX 77030. Tel.: 713-500-5621; Fax: 713-500-0621; E-mail: m.n.waxham{at}uth.tmc.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. J. Saucerman and D. M. Bers Calmodulin Mediates Differential Sensitivity of CaMKII and Calcineurin to Local Ca2+ in Cardiac Myocytes Biophys. J., November 15, 2008; 95(10): 4597 - 4612. [Abstract] [Full Text] [PDF]

				Q. Song, J. J. Saucerman, J. Bossuyt, and D. M. Bers Differential Integration of Ca2+-Calmodulin Signal in Intact Ventricular Myocytes at Low and High Affinity Ca2+-Calmodulin Targets J. Biol. Chem., November 14, 2008; 283(46): 31531 - 31540. [Abstract] [Full Text] [PDF]

				H. Y. Park, S. A. Kim, J. Korlach, E. Rhoades, L. W. Kwok, W. R. Zipfel, M. N. Waxham, W. W. Webb, and L. Pollack Conformational changes of calmodulin upon Ca2+ binding studied with a microfluidic mixer PNAS, January 15, 2008; 105(2): 542 - 547. [Abstract] [Full Text] [PDF]

				Y. Kubota, J. A. Putkey, H. Z. Shouval, and M. N. Waxham IQ-Motif Proteins Influence Intracellular Free Ca2+ in Hippocampal Neurons Through Their Interactions With Calmodulin J Neurophysiol, January 1, 2008; 99(1): 264 - 276. [Abstract] [Full Text] [PDF]

				Y. Kubota, J. A. Putkey, and M. N. Waxham Neurogranin Controls the Spatiotemporal Pattern of Postsynaptic Ca2+/CaM Signaling Biophys. J., December 1, 2007; 93(11): 3848 - 3859. [Abstract] [Full Text] [PDF]

				R. E. Simpson, A. Ciruela, and D. M. F. Cooper The Role of Calmodulin Recruitment in Ca2+ Stimulation of Adenylyl Cyclase Type 8 J. Biol. Chem., June 23, 2006; 281(25): 17379 - 17389. [Abstract] [Full Text] [PDF]

				X. Luo, Q. He, Y. Huang, and M. S. Sheikh Cloning and Characterization of a p53 and DNA Damage Down-regulated Gene PIQ that Codes for a Novel Calmodulin-Binding IQ Motif Protein and Is Up-regulated in Gastrointestinal Cancers Cancer Res., December 1, 2005; 65(23): 10725 - 10733. [Abstract] [Full Text] [PDF]