title: The multiple faces of calcineurin signaling in Caenorhabditis elegans: development, behaviour and aging.
abstract: Calcineurin, a well-conserved protein phosphatase 2B (PP2B), is a Ca2+-calmodulin-dependent serine/threonine protein phosphatase that is known to be involved in a myriad of cellular processes and signal transduction pathways. The biological role of calcineurin has been extensively studied in diverse groups of organisms. Homologues of mammalian and Drosophila calcineurin subunits exist in the nematode, Caenorhabditis elegans. The C. elegans counterpart of the catalytic subunit, calcineurin A, cna-1/tax-6, and the regulatory subunit, calcineurin B, cnb-1, are known to express ubiquitously in multiple tissues including neurons. The characterization of C. elegans calcineurin mutants facilitates identification of its physiological functions and signaling pathways. Genetic interactions between cna-1/tax-6 and cnb-1 mutants with a number of mutants involved in several signaling pathways have exemplified the pivotal role of calcineurin in regulating nematode development, behaviour and lifespan (aging). The present review has been aimed to provide a succinct summary of the multiple functions of calcineurin in C. elegans relating to its development, fertility, proliferation, behaviour and lifespan. Analyses of cna-1/tax-6 and cnb-1 interacting proteins and regulators of the phosphatase in this fascinating worm model have an immense scope to identify potential drug targets in various parasitic nematodes, which cause many diseases inflicting huge economic loss; and also for many human diseases, particularly neurodegenerative and myocardial diseases.
authors: Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N, Seattle, WA 98109, USA.
authors: Jin Il
authors: JI
authors: Lee
authors: Sutapa
authors: S
authors: Mukherjee
authors: Kyoung-Hye
authors: KH
authors: Yoon
authors: Meenakshi
authors: M
authors: Dwivedi
authors: Jaya
authors: J
authors: Bandyopadhyay
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal; D017173:Caenorhabditis elegans / Q000378:metabolism / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D019703:Calcineurin / Q000378:metabolism*; D020013:Calcium Signaling; D048788:Growth and Development; D006801:Humans; D012098:Reproduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D019703:Calcineurin
references: Curr Biol. 2007 Oct 9;17(19):1635-45
references: 17900898
references: J Biol Chem. 1998 May 29;273(22):13367-70
references: 9593662
references: EMBO J. 1992 Nov;11(11):3857-63
references: 1396579
references: Dev Biol. 1977 Mar;56(1):110-56
references: 838129
references: Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):8044-9
references: 18524954
references: Nature. 1994 Dec 22-29;372(6508):780-3
references: 7997265
references: Physiol Rev. 2000 Oct;80(4):1483-521
references: 11015619
references: Exp Neurol. 2001 Jan;167(1):158-65
references: 11161603
references: Nature. 2007 Jul 19;448(7151):375-9
references: 17637672
references: Exp Gerontol. 2008 Jan;43(1):1-4
references: 17977684
references: Nat Neurosci. 2003 Nov;6(11):1145-52
references: 14555952
references: Nature. 2009 Jul 23;460(7254):534-7
references: 19543265
references: Nature. 2004 Jul 15;430(6997):317-22
references: 15220933
references: Science. 2003 Sep 5;301(5638):1387-91
references: 12958363
references: Proc Natl Acad Sci U S A. 2003 Jul 22;100(15):8987-92
references: 12851457
references: Cell. 1996 Jan 12;84(1):115-25
references: 8548815
references: EMBO J. 1990 Dec;9(13):4425-33
references: 1702384
references: Mech Ageing Dev. 1983 Jul-Aug;22(3-4):279-86
references: 6632998
references: Cell. 1995 Jan 27;80(2):225-36
references: 7834742
references: Mol Biol Cell. 2002 Sep;13(9):3281-93
references: 12221132
references: Genes Dev. 2003 Aug 1;17(15):1882-93
references: 12869585
references: Cell. 2004 Oct 1;119(1):61-74
references: 15454081
references: Cell. 1998 Jan 9;92(1):39-49
references: 9489698
references: J Neurochem. 1992 May;58(5):1643-51
references: 1313851
references: Ann N Y Acad Sci. 2010 Aug;1204:156-62
references: 20738286
references: Annu Rev Genet. 2006;40:487-509
references: 17094742
references: Genetics. 2007 Sep;177(1):655-60
references: 17890369
references: Nature. 1991 Aug 29;352(6338):803-7
references: 1715516
references: Nat Rev Mol Cell Biol. 2001 Aug;2(8):599-609
references: 11483993
references: BMC Dev Biol. 2006 Aug 03;6:39
references: 16884547
references: Autophagy. 2012 Jan;8(1):144-6
references: 22186228
references: Science. 2000 Dec 1;290(5497):1717-21
references: 11099404
references: Genes Dev. 2000 Jul 1;14(13):1595-604
references: 10887154
references: Acta Med Okayama. 2007 Jun;61(3):123-37
references: 17593948
references: J Biol Chem. 1998 Sep 11;273(37):23877-83
references: 9727000
references: Metallomics. 2011 Mar;3(3):271-9
references: 21210060
references: Biochemistry. 1978 Jan 10;17(1):120-6
references: 201280
references: J Biol Chem. 2003 Dec 26;278(52):52340-6
references: 14559923
references: Proc Natl Acad Sci U S A. 2000 May 9;97(10):5285-90
references: 10805788
references: Trends Cell Biol. 2009 Oct;19(10):487-94
references: 19726187
references: Curr Biol. 2003 Oct 28;13(21):1910-5
references: 14588249
references: Mol Cells. 2009 Nov 30;28(5):455-61
references: 19855932
references: Cell. 1988 Nov 18;55(4):555-65
references: 3180220
references: J Mol Biol. 2012 Mar 30;417(3):165-78
references: 22300764
references: Cell. 1993 Dec 3;75(5):827-30
references: 8252617
references: Mol Cell Biol. 2000 Jan;20(2):429-40
references: 10611221
references: J Neurochem. 1985 Jul;45(1):276-83
references: 2987415
references: Annu Rev Immunol. 1997;15:707-47
references: 9143705
references: J Mol Biol. 2004 Nov 19;344(2):585-95
references: 15522306
references: Clin Biochem. 2007 Apr;40(7):443-6
references: 17328882
references: Mol Biochem Parasitol. 2005 Jan;139(1):51-64
references: 15610819
references: Development. 2000 Oct;127(19):4239-52
references: 10976055
references: Neuron. 2002 Feb 28;33(5):751-63
references: 11879652
references: Proc Natl Acad Sci U S A. 2005 Mar 22;102(12):4494-9
references: 15767565
references: Genetics. 1995 Apr;139(4):1567-83
references: 7789761
references: Nature. 2003 Dec 11;426(6967):620
references: 14668850
references: Autophagy. 2007 Mar-Apr;3(2):93-5
references: 17204841
references: Proc Natl Acad Sci U S A. 2001 May 8;98(10):5740-5
references: 11344309
references: J Neurosci. 2006 Sep 13;26(37):9355-64
references: 16971519
references: Trends Genet. 2008 Dec;24(12):604-12
references: 18992957
references: Biochem Biophys Res Commun. 2007 Jan 5;352(1):29-35
references: 17113567
references: BMB Rep. 2008 Jun 30;41(6):455-60
references: 18593529
references: Genetics. 1995 Dec;141(4):1399-406
references: 8601482
references: Dev Biol. 1983 Nov;100(1):64-119
references: 6684600
references: Proc Natl Acad Sci U S A. 2004 Mar 2;101(9):2870-5
references: 14976250
references: Science. 2007 Aug 3;317(5838):660-3
references: 17673661
references: Cell. 1998 Jan 9;92(1):25-37
references: 9489697
references: Dev Biol. 2004 Feb 1;266(1):1-16
references: 14729474
references: Genetics. 2001 Apr;157(4):1599-610
references: 11290716
references: J Mol Biol. 2005 Sep 16;352(2):313-8
references: 16084527
references: J Neurosci. 2003 Feb 1;23(3):826-36
references: 12574411
references: EMBO J. 2006 Jan 25;25(2):312-22
references: 16407969
references: Science. 2003 Feb 28;299(5611):1351-4
references: 12610295
references: Oncogene. 2000 Jun 1;19(24):2820-7
references: 10851085
references: Mol Cells. 2008 Jun 30;25(4):566-71
references: 18460897
references: Nature. 2011 Feb 17;470(7334):404-8
references: 21331044
references: Mol Cells. 2004 Aug 31;18(1):10-6
references: 15359118
references: Genetics. 1974 May;77(1):71-94
references: 4366476
references: Science. 2006 Aug 18;313(5789):971-5
references: 16917064
references: Nature. 2005 Oct 20;437(7062):1109-11
references: 16148943
references: Proc Natl Acad Sci U S A. 2008 Jun 10;105(23):8038-43
references: 18524955
references: Proc Natl Acad Sci U S A. 1975 Oct;72(10):4061-5
references: 1060088
references: Science. 1995 Mar 17;267(5204):1652-5
references: 7886455
references: Cell. 1999 Mar 5;96(5):611-4
references: 10089876
references: Cell. 2006 Jun 16;125(6):1165-77
references: 16777605
references: Neurosci Res. 2009 Jul;64(3):280-9
references: 19447297
references: Mol Biol Cell. 2006 May;17(5):2200-11
references: 16481400
references: Genetics. 2003 Dec;165(4):1805-22
references: 14704167
references: Trends Cell Biol. 2007 Sep;17(9):422-7
references: 17804237
references: Cell. 1998 Apr 17;93(2):215-28
references: 9568714
references: J Biol Chem. 1998 Jul 17;273(29):18325-31
references: 9660798
references: Nature. 2007 May 31;447(7144):550-5
references: 17476212
references: Nature. 2008 Jan 31;451(7178):569-72
references: 18185515
references: FASEB J. 2010 Dec;24(12):4977-88
references: 20732954
references: BMC Genet. 2010 Jan 27;11:7
references: 20105303
references: Genetics. 2000 Nov;156(3):1069-82
references: 11063685
references: Proc Natl Acad Sci U S A. 1979 Dec;76(12):6270-3
references: 293720
references: Cell. 1995 Jan 27;80(2):259-68
references: 7834745
references: Neurobiol Learn Mem. 2002 May;77(3):291-312
references: 11991759
references: J Am Soc Nephrol. 2004 Jun;15(6):1421-9
references: 15153553
references: Curr Opin Cell Biol. 2005 Dec;17(6):604-9
references: 16226450
references: Biochem Biophys Res Commun. 1999 Jul 14;260(3):619-25
references: 10403816
references: J Exp Biol. 2008 Dec;211(Pt 23):3703-11
references: 19011210
references: J Mol Biol. 2003 Apr 18;328(1):147-56
references: 12684004
references: Proteomics. 2006 Feb;6(4):1340-50
references: 16402360
references: Genetics. 1983 Aug;104(4):619-47
references: 11813735
references: Immunity. 1998 Jun;8(6):703-11
references: 9655484
references: Neuron. 1998 Mar;20(3):445-68
references: 9539121
references: Learn Mem. 2012 Aug 16;19(9):375-84
references: 22904368
references: Cell. 1991 Aug 23;66(4):807-15
references: 1715244
references: Mech Ageing Dev. 2001 May 31;122(7):571-94
references: 11322988
references: Ageing Res Rev. 2003 Oct;2(4):451-71
references: 14522246
references: Autophagy. 2009 Jul;5(5):604-7
references: 19279398
references: Biochem Biophys Res Commun. 2003 Nov 28;311(4):1095-102
references: 14623295
references: J Biol Chem. 1999 Dec 17;274(51):36125-31
references: 10593895
references: J Neuropathol Exp Neurol. 1996 Aug;55(8):924-31
references: 8759782
references: Autophagy. 2008 Apr;4(3):330-8
references: 18219227
references: Hum Mol Genet. 2000 Jul 1;9(11):1681-90
references: 10861295
references: Genetics. 1986 Jul;113(3):621-39
references: 3732788
references: J Biol Chem. 2001 Jan 26;276(4):2313-6
references: 11096121
references: Proc Natl Acad Sci U S A. 2011 Jan 4;108(1):254-9
references: 21173231
references: FEBS Lett. 1982 Jan 11;137(1):80-4
references: 6279434
references: Adv Second Messenger Phosphoprotein Res. 1993;27:1-23
references: 8380326
references: Biochem Biophys Res Commun. 1976 Oct 4;72(3):926-32
references: 186066
references: EMBO J. 2005 Jul 20;24(14):2566-78
references: 15990870
references: FEBS Lett. 2010 Apr 2;584(7):1335-41
references: 20138173
references: Autophagy. 2008 Oct;4(7):870-3
references: 18728385
references: Curr Biol. 2005 May 24;15(10):905-17
references: 15916947