Research article summary (published 22 Oct 2007):

IQ-motif proteins influence intracellular free Ca2+ in hippocampal neurons through their interactions with calmodulin.

Full Abstract

Calmodulin (CaM) is most recognized for its role in activating Ca(2+)-CaM-dependent enzymes following increased intracellular Ca(2+). However, CaM's high intracellular concentration indicates CaM has the potential to play a significant role as a Ca(2+) buffer. Neurogranin (Ng) is a small neuronal IQ-motif-containing protein that accelerates Ca(2+) dissociation from CaM. In cells that contain high concentrations of both Ng and CaM, like CA1 pyramidal neurons, we hypothesize that the accelerated Ca(2+) dissociation from CaM by Ng decreases the buffering capacity of CaM and thereby shapes the transient dynamics of intracellular free Ca(2+). We examined this hypothesis using a mathematical model constructed on the known biochemistry of Ng and confirmed the simulation results with Ca(2+) imaging data in the literature. In a single-compartment model that contains no Ca(2+) extrusion mechanism, Ng increased the steady-state free Ca(2+). However, in the presence of a Ca(2+) extrusion mechanism, Ng accelerated the decay rate of free Ca(2+) through its ability to increase the Ca(2+) dissociation from CaM, which in turn becomes subject to Ca(2+) extrusion. Interestingly, PEP-19, another neuronal IQ-motif protein that accelerates both Ca(2+) association and dissociation from CaM, appears to have the opposite impact than that of Ng on free Ca(2+). As such, Ng may regulate, in addition to the Ca(2+)-CaM-dependent process, Ca(2+)-sensitive enzymes by influencing the buffering capacity of CaM and subsequently free Ca(2+) levels. We examined the relative impact of these Ng-induced effects in the induction of synaptic plasticity.

Author information

Author/s: Kubota, Yoshihisa (Y); Putkey, John A (JA); Shouval, Harel Z (HZ); Waxham, M Neal (MN);

Affiliation: Department of Neurobiology and Anatomy, University of Texas Medical School, 6431 Fannin, Houston, Texas 77030, USA. Yoshihisa.Kubota(-atsign-)uth.tmc.edu

Grants: GM-069611 (Agency:NIGMS NIH HHS) ; NS-038310 (Agency:NINDS NIH HHS) ; NS-041226 (Agency:NINDS NIH HHS)

Journal and publication information

Publication Type: Journal Article; Research Support, N.I.H., Extramural

Journal: Journal of neurophysiology (J Neurophysiol), published in United States. (Language: eng)

Reference: 2008-Jan; vol 99 (issue 1) : pp 264-76

Dates: Created 2008/01/15; Completed 2008/03/24;

PMID: 17959737, status: MEDLINE (last retrieved date: 2/18/2009)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MeSH Headings (categories) shown below.

Action Potentials - physiology Amino Acid Motifs - physiology Animals Buffers Calcium - metabolism Calcium Signaling - physiology Calmodulin - metabolism Computer Simulation Cytoplasm - metabolism Hippocampus - metabolism Humans

Humans Intracellular Fluid - metabolism Mice Mice, Knockout Models, Neurological Nerve Tissue Proteins - metabolism Neurogranin - chemistry; genetics; metabolism Neuronal Plasticity - physiology Neurons - metabolism Synaptic Transmission - physiology Up-Regulation - physiology

Note: Bold headings indicate primary MeSH headings or qualifiers.

Associated Chemicals: Buffers (0) ; Calmodulin (0) ; Nerve Tissue Proteins (0) ; Pcp4 protein, mouse (0) ; Neurogranin (132654-77-4) ; Calcium (7440-70-2)

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