title: Neurogranin controls the spatiotemporal pattern of postsynaptic Ca2+/CaM signaling.
abstract: Neurogranin (Ng) is a postsynaptic IQ-motif containing protein that accelerates Ca(2+) dissociation from calmodulin (CaM), a key regulator of long-term potentiation and long-term depression in CA1 pyramidal neurons. The exact physiological role of Ng, however, remains controversial. Two genetic knockout studies of Ng showed opposite outcomes in terms of the induction of synaptic plasticity. To understand its function, we test the hypothesis that Ng could regulate the spatial range of action of Ca(2+)/CaM based on its ability to accelerate the dissociation of Ca(2+) from CaM. Using a mathematical model constructed on the known biochemistry of Ng, we calculate the cycle time that CaM molecules alternate between the fully Ca(2+) saturated state and the Ca(2+) unbound state. We then use these results and include diffusion of CaM to illustrate the impact that Ng has on modulating the spatial profile of Ca(2+)-saturated CaM within a model spine compartment. Finally, the first-passage time of CaM to transition from the Ca(2+)-free state to the Ca(2+)-saturated state was calculated with or without Ng present. These analyses suggest that Ng regulates the encounter rate between Ca(2+) saturated CaM and its downstream targets during postsynaptic Ca(2+) transients.
authors: Department of Neurobiology and Anatomy, and Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston, Texas, USA. Yoshihisa.Kubota@uth.tmc.edu
authors: Yoshihisa
authors: Y
authors: Kubota
authors: John A
authors: JA
authors: Putkey
authors: M Neal
authors: MN
authors: Waxham
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002147:Calmodulin / Q000378:metabolism*; D003198:Computer Simulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D006801:Humans; D008959:Models, Neurological; D051579:Neurogranin / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism; D017966:Pyramidal Cells / Q000502:physiology*
chemical_list: D002147:Calmodulin; D018377:Neurotransmitter Agents; D051579:Neurogranin; D002118:Calcium
references: Neuron. 2002 Jan 31;33(3):439-52
references: 11832230
references: Cell Calcium. 2006 Nov-Dec;40(5-6):405-12
references: 17030366
references: Bioessays. 2002 Dec;24(12):1130-44
references: 12447978
references: Biophys J. 2003 Feb;84(2 Pt 1):1065-78
references: 12547788
references: J Biol Chem. 2003 Dec 12;278(50):49667-70
references: 14551202
references: Proc Natl Acad Sci U S A. 2004 Jan 6;101(1):105-10
references: 14695888
references: J Biol Chem. 2004 Sep 17;279(38):39374-82
references: 15262982
references: Nature. 1985 May 2-8;315(6014):37-40
references: 3990807
references: J Neurosci. 1989 Aug;9(8):2982-97
references: 2769375
references: Nature. 1989 Aug 17;340(6234):554-7
references: 2549423
references: Neuron. 1994 May;12(5):943-56
references: 8185953
references: J Biol Chem. 1994 Sep 2;269(35):22420-6
references: 8071370
references: Cold Spring Harb Symp Quant Biol. 1995;60:793-802
references: 8824454
references: Science. 1999 Jan 15;283(5400):381-7
references: 9888852
references: J Neurophysiol. 1999 Feb;81(2):781-7
references: 10036277
references: J Neurosci Res. 1999 Oct 1;58(1):107-19
references: 10491576
references: J Neurosci. 2004 Nov 24;24(47):10660-9
references: 15564582
references: Biophys J. 2005 Apr;88(4):2494-515
references: 15681642
references: Nat Rev Neurosci. 2005 Apr;6(4):267-76
references: 15803158
references: Biochem Biophys Res Commun. 2005 Aug 26;334(2):674-80
references: 16009337
references: Biophys J. 2005 Oct;89(4):2277-85
references: 16040752
references: Phys Biol. 2004 Dec;1(3-4):137-51
references: 16204833
references: J Neurosci. 2006 Jul 12;26(28):7337-47
references: 16837580
references: J Neurosci. 2002 Jul 1;22(13):5525-35
references: 12097504