Ca2+-dependent facilitation of Cav1.3 Ca2+ channels by densin and Ca2+/calmodulin-dependent protein kinase II.
Ca(v)1 (L-type) channels and calmodulin-dependent protein kinase II (CaMKII) are key regulators of Ca(2+) signaling in neurons. CaMKII directly potentiates the activity of Ca(v)1.2 and Ca(v)1.3 channels, but the underlying molecular mechanisms are incompletely understood. Here, we report that the CaMKII-associated protein densin is required for Ca(2+)-dependent facilitation of Ca(v)1.3 channels. While neither CaMKII nor densin independently affects Ca(v)1.3 properties in transfected HEK293T cells, the two together augment Ca(v)1.3 Ca(2+) currents during repetitive, but not sustained, depolarizing stimuli. Facilitation requires Ca(2+), CaMKII activation, and its association with densin, as well as densin binding to the Ca(v)1.3 alpha(1) subunit C-terminal domain. Ca(v)1.3 channels and densin are targeted to dendritic spines in neurons and form a complex with CaMKII in the brain. Our results demonstrate a novel mechanism for Ca(2+)-dependent facilitation that may intensify postsynaptic Ca(2+) signals during high-frequency stimulation.
Jenkins
Meagan A
MA
Department of Pharmacology, Emory University, Atlanta, Georgia 30322, USA.
Christel
Carl J
CJ
Jiao
Yuxia
Y
Abiria
Sunday
S
Kim
Kristin Y
KY
Usachev
Yuriy M
YM
Obermair
Gerald J
GJ
Colbran
Roger J
RJ
Lee
Amy
A
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism*; D002460:Cell Line; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000201:enzymology / Q000378:metabolism; D006624:Hippocampus / Q000201:enzymology / Q000378:metabolism; D006801:Humans; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000201:enzymology / Q000378:metabolism; D051381:Rats; D012795:Sialoglycoproteins / Q000378:metabolism*; D014162:Transfection
D015220:Calcium Channels; C504463:Lrrc7 protein, rat; D012795:Sialoglycoproteins; C093712:Cacna1d protein, rat; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D002118:Calcium
J Neurosci. 2006 Oct 18;26(42):10677-89
17050707
J Neurosci. 2006 Jun 7;26(23):6259-68
16763033
Biochem Biophys Res Commun. 2006 Jul 14;345(4):1606-10
16730662
Curr Opin Neurobiol. 2004 Jun;14(3):318-27
15194112
Eur J Neurosci. 2004 Apr;19(8):2109-22
15090038
J Neurochem. 2010 Jan;112(1):150-61
19840220
Mol Endocrinol. 2001 Jul;15(7):1211-21
11435619
Biochem Biophys Res Commun. 1990 Dec 14;173(2):578-84
2175600
Nature. 2009 Mar 19;458(7236):299-304
19295602
Nat Cell Biol. 2000 Jul;2(7):E114
10878817
Eur J Neurosci. 2005 Jul;22(1):247-56
16029214
J Biol Chem. 2002 Feb 15;277(7):5345-50
11729199
J Neurosci. 2005 Nov 2;25(44):10247-51
16267232
Science. 1992 May 22;256(5060):1199-202
1317063
Trends Neurosci. 2009 May;32(5):249-56
19307031
Sci STKE. 2006 Jan 17;2006(318):er1
16685765
Proc Natl Acad Sci U S A. 1987 Jun;84(11):3941-5
2438689
J Neurosci. 2005 Feb 2;25(5):1050-62
15689540
J Physiol. 1982 Aug;329:589-614
6292410
J Biol Chem. 2001 Jun 22;276(25):22100-6
11285265
Learn Mem. 2006 Sep-Oct;13(5):584-9
17015855
Neuron. 2007 Jul 19;55(2):261-75
17640527
Nature. 2008 Feb 14;451(7180):830-4
18235447
Nat Cell Biol. 2000 Mar;2(3):173-7
10707089
J Biol Chem. 1992 Jan 25;267(3):1792-7
1370480
Nat Rev Neurosci. 2002 Mar;3(3):175-90
11994750
J Neurosci. 2004 Sep 29;24(39):8394-8
15456810
J Neurosci. 1996 Nov 1;16(21):6839-52
8824323
Neuron. 2009 Feb 12;61(3):351-8
19217373
J Biol Chem. 2000 Aug 18;275(33):25061-4
10827168
Proc Natl Acad Sci U S A. 2003 Oct 28;100(22):13093-8
14569017
Annu Rev Biochem. 2002;71:473-510
12045104
Genes Cells. 2002 Nov;7(11):1149-60
12390249
Neuron. 1994 May;12(5):943-56
8185953
J Neurochem. 2008 May;105(3):573-83
18266933
J Neurosci. 2001 Aug 15;21(16):5944-51
11487617
Science. 1998 Jan 9;279(5348):227-30
9422695
J Biol Chem. 2010 Feb 19;285(8):5776-91
19996312
Biochemistry. 1980 May 27;19(11):2396-404
6770893
J Physiol. 1981 Jan;310:57-75
6785423
J Cell Biol. 2005 Nov 7;171(3):537-47
16275756
J Neurosci. 2007 Feb 7;27(6):1374-85
17287512
Proc Natl Acad Sci U S A. 2005 May 31;102(22):8042-7
15901899
J Neurosci. 2007 Jan 17;27(3):645-56
17234596
J Neurosci. 2004 Jun 9;24(23):5283-91
15190099
Science. 1997 Jan 3;275(5296):73-7
8974395
J Biol Chem. 2005 Oct 21;280(42):35329-36
16120608
J Clin Invest. 2004 May;113(10):1430-9
15146240
Eur J Neurosci. 2006 May;23(9):2297-310
16706838
Nat Neurosci. 2006 Feb;9(2):251-9
16415865
J Biol Chem. 2006 Sep 1;281(35):25560-7
16820363
J Neurosci. 2005 Jan 12;25(2):479-87
15647492
J Neurochem. 2008 Jun;105(5):1746-60
18248607
J Cell Biol. 2003 Jul 7;162(1):99-111
12835311
J Neurosci. 2001 Jan 15;21(2):423-33
11160423
Science. 1978 Dec 15;202(4373):1203-6
103199
J Cell Biol. 2008 Dec 1;183(5):849-63
19047462
J Mol Cell Cardiol. 2004 Sep;37(3):625-31
15350835
Nature. 2007 Jun 28;447(7148):1081-6
17558391
Mol Cell. 2006 Sep 1;23(5):641-50
16949361
J Biol Chem. 1995 Apr 28;270(17):10043-9
7730306
J Biol Chem. 2000 Jul 14;275(28):21121-9
10779517
Nat Neurosci. 2003 Sep;6(9):948-55
12937422
Biochemistry. 2008 Feb 12;47(6):1760-7
18205403
Nature. 1999 May 13;399(6732):159-62
10335846
Proc Natl Acad Sci U S A. 1998 Sep 1;95(18):10890-5
9724800
J Physiol. 2001 Sep 15;535(Pt 3):679-87
11559766
J Biol Chem. 2002 Sep 13;277(37):33598-603
12114507
Biochim Biophys Acta. 1996 Oct 17;1297(2):131-8
8917614