title: Characterization of a central Ca2+/calmodulin-dependent protein kinase IIalpha/beta binding domain in densin that selectively modulates glutamate receptor subunit phosphorylation.
abstract: The densin C-terminal domain can target Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα) in cells. Although the C-terminal domain selectively binds CaMKIIα in vitro, full-length densin associates with CaMKIIα or CaMKIIβ in brain extracts and in transfected HEK293 cells. This interaction requires a second central CaMKII binding site, the densin-IN domain, and an "open" activated CaMKII conformation caused by Ca(2+)/calmodulin binding, autophosphorylation at Thr-286/287, or mutation of Thr-286/287 to Asp. Mutations in the densin-IN domain (L815E) or in the CaMKIIα/β catalytic domain (I205/206K) disrupt the interaction. The amino acid sequence of the densin-IN domain is similar to the CaMKII inhibitor protein, CaMKIIN, and a CaMKIIN peptide competitively blocks CaMKII binding to densin. CaMKII is inhibited by both CaMKIIN and the densin-IN domain, but the inhibition by densin is substrate-selective. Phosphorylation of a model peptide substrate, syntide-2, or of Ser-831 in AMPA receptor GluA1 subunits is fully inhibited by densin. However, CaMKII phosphorylation of Ser-1303 in NMDA receptor GluN2B subunits is not effectively inhibited by densin in vitro or in intact cells. Thus, densin can target multiple CaMKII isoforms to differentially modulate phosphorylation of physiologically relevant downstream targets.
authors: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
authors: Yuxia
authors: Y
authors: Jiao
authors: Nidhi
authors: N
authors: Jalan-Sakrikar
authors: A J
authors: AJ
authors: Robison
authors: Anthony J
authors: AJ
authors: Baucum
authors: Martha A
authors: MA
authors: Bass
authors: Roger J
authors: RJ
authors: Colbran
references: Cell. 2005 Dec 2;123(5):849-60
references: 16325579
references: J Neurosci. 1999 Sep 15;19(18):7823-33
references: 10479685
references: J Neurosci. 2007 Dec 12;27(50):13843-53
references: 18077696
references: Biochem J. 2004 Feb 15;378(Pt 1):1-16
references: 14653781
references: J Cell Biol. 1994 Aug;126(4):839-52
references: 7519621
references: J Biol Chem. 2005 Oct 21;280(42):35329-36
references: 16120608
references: Trends Biochem Sci. 2010 Aug;35(8):450-8
references: 20399103
references: J Biol Chem. 1985 Feb 10;260(3):1696-704
references: 3968085
references: Proc Natl Acad Sci U S A. 2010 Aug 10;107(32):14437-42
references: 20660727
references: Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10890-5
references: 9724800
references: Cell. 2010 Feb 19;140(4):567-78
references: 20178748
references: J Neurosci. 2006 Jan 25;26(4):1164-74
references: 16436603
references: Neuron. 2002 Dec 19;36(6):1103-14
references: 12495625
references: PLoS Biol. 2010 Jul 27;8(7):e1000426
references: 20668654
references: J Neurosci. 2010 Apr 14;30(15):5125-35
references: 20392935
references: J Neurosci. 2004 Sep 29;24(39):8399-403
references: 15456811
references: J Biol Chem. 1998 Aug 14;273(33):20689-92
references: 9694809
references: J Biol Chem. 2002 Feb 15;277(7):5345-50
references: 11729199
references: J Neurosci. 1995 Oct;15(10):6797-808
references: 7472438
references: Nat Rev Mol Cell Biol. 2004 Dec;5(12):959-70
references: 15573134
references: Neuron. 1998 Sep;21(3):593-606
references: 9768845
references: J Neurosci. 1996 Nov 1;16(21):6839-52
references: 8824323
references: J Biol Chem. 2000 Aug 18;275(33):25061-4
references: 10827168
references: J Biol Chem. 1989 Oct 25;264(30):17907-12
references: 2553697
references: J Biol Chem. 1985 Jul 25;260(15):9039-46
references: 4019461
references: Mol Biol Cell. 2007 Dec;18(12):5024-33
references: 17942605
references: J Biol Chem. 1997 Dec 26;272(52):32727-30
references: 9407043
references: Nature. 2001 Jun 14;411(6839):801-5
references: 11459059
references: J Biol Chem. 1999 Sep 10;274(37):26199-208
references: 10473573
references: J Biol Chem. 2000 Aug 4;275(31):23798-806
references: 10764765
references: J Biol Chem. 1996 Dec 6;271(49):31670-8
references: 8940188
references: Nat Neurosci. 2007 Sep;10(9):1125-7
references: 17660813
references: Neuron. 2005 Oct 20;48(2):289-301
references: 16242409
references: Nat Struct Mol Biol. 2010 Mar;17(3):264-72
references: 20139983
references: Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15791-6
references: 18840684
references: J Neurosci. 2005 Jan 12;25(2):479-87
references: 15647492
references: J Neurochem. 2008 Jun;105(5):1746-60
references: 18248607
references: J Biol Chem. 1999 Aug 6;274(32):22713-22
references: 10428854
references: J Neurosci. 2001 Jan 15;21(2):423-33
references: 11160423
references: J Biol Chem. 2005 Nov 25;280(47):39316-23
references: 16172120
references: Nat Struct Mol Biol. 2010 Jun;17(6):653-8
references: 20495562
references: Mol Cell. 2006 Sep 1;23(5):641-50
references: 16949361
references: J Neurochem. 2009 Apr;109(2):297-302
references: 19187442
references: Biochemistry. 2008 Feb 12;47(6):1760-7
references: 18205403
references: J Biol Chem. 2010 Jan 8;285(2):923-34
references: 19858198
references: Neuron. 2001 May;30(2):489-502
references: 11395009