title: Connexin 39.9 protein is necessary for coordinated activation of slow-twitch muscle and normal behavior in zebrafish.
abstract: In many tissues and organs, connexin proteins assemble between neighboring cells to form gap junctions. These gap junctions facilitate direct intercellular communication between adjoining cells, allowing for the transmission of both chemical and electrical signals. In rodents, gap junctions are found in differentiating myoblasts and are important for myogenesis. Although gap junctions were once believed to be absent from differentiated skeletal muscle in mammals, recent studies in teleosts revealed that differentiated muscle does express connexins and is electrically coupled, at least at the larval stage. These findings raised questions regarding the functional significance of gap junctions in differentiated muscle. Our analysis of gap junctions in muscle began with the isolation of a zebrafish motor mutant that displayed weak coiling at day 1 of development, a behavior known to be driven by slow-twitch muscle (slow muscle). We identified a missense mutation in the gene encoding Connexin 39.9. In situ hybridization found connexin 39.9 to be expressed by slow muscle. Paired muscle recordings uncovered that wild-type slow muscles are electrically coupled, whereas mutant slow muscles are not. The further examination of cellular activity revealed aberrant, arrhythmic touch-evoked Ca(2+) transients in mutant slow muscle and a reduction in the number of muscle fibers contracting in response to touch in mutants. These results indicate that Connexin 39.9 facilitates the spreading of neuronal inputs, which is irregular during motor development, beyond the muscle cells and that gap junctions play an essential role in the efficient recruitment of slow muscle fibers.
authors.affiliation: Center for Frontier Research, National Institute of Genetics, Mishima 411-8540, Japan. hihirata@lab.nig.ac.jp
authors.forename: Hiromi
authors.initials: H
authors.lastname: Hirata
authors.forename: Hua
authors.initials: H
authors.lastname: Wen
authors.forename: Yu
authors.initials: Y
authors.lastname: Kawakami
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Naganawa
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Ogino
authors.forename: Kenta
authors.initials: K
authors.lastname: Yamada
authors.forename: Louis
authors.initials: L
authors.lastname: Saint-Amant
authors.forename: Sean E
authors.initials: SE
authors.lastname: Low
authors.forename: Wilson W
authors.initials: WW
authors.lastname: Cui
authors.forename: Weibin
authors.initials: W
authors.lastname: Zhou
authors.forename: Shawn M
authors.initials: SM
authors.lastname: Sprague
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Asakawa
authors.forename: Akira
authors.initials: A
authors.lastname: Muto
authors.forename: Koichi
authors.initials: K
authors.lastname: Kawakami
authors.forename: John Y
authors.initials: JY
authors.lastname: Kuwada
mesh_terms: D000818:Animals; D001483:Base Sequence; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D017629:Gap Junctions / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D008969:Molecular Sequence Data; D018657:Muscle Fibers, Slow-Twitch; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense; D015027:Zebrafish / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D017630:Connexins; D009124:Muscle Proteins; D029961:Zebrafish Proteins
references.citation: Biochim Biophys Acta. 2007 Feb;1772(2):205-15
references.pmid: 16934958
references.citation: J Neurophysiol. 1999 Jun;81(6):2852-61
references.pmid: 10368402
references.citation: Dev Growth Differ. 2007 Jan;49(1):1-11
references.pmid: 17227340
references.citation: Dev Dyn. 2005 Jul;233(3):890-906
references.pmid: 15895415
references.citation: J Exp Biol. 2004 Feb;207(Pt 5):853-68
references.pmid: 14747416
references.citation: Dev Biol. 1973 Jan;30(1):166-86
references.pmid: 4735364
references.citation: Cell Commun Adhes. 2003 Jan-Feb;10(1):27-36
references.pmid: 12881038
references.citation: J Gen Physiol. 2006 Jul;128(1):89-102
references.pmid: 16801383
references.citation: Annu Rev Physiol. 1999;61:283-310
references.pmid: 10099690
references.citation: Cell Mol Life Sci. 2006 May;63(10):1125-40
references.pmid: 16568237
references.citation: Development. 1996 Dec;123:399-413
references.pmid: 9007258
references.citation: Development. 2004 Nov;131(21):5457-68
references.pmid: 15469975
references.citation: J Neurophysiol. 2000 Sep;84(3):1545-57
references.pmid: 10980026
references.citation: Genomics. 1999 Jun 15;58(3):219-32
references.pmid: 10373319
references.citation: J Cell Biol. 1977 Dec;75(3):788-806
references.pmid: 925080
references.citation: FEBS Lett. 2009 Nov 3;583(21):3419-24
references.pmid: 19808035
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 7;102(23):8345-50
references.pmid: 15928085
references.citation: Cell Calcium. 2006 Mar;39(3):227-36
references.pmid: 16368137
references.citation: J Neurobiol. 2006 Apr;66(5):437-51
references.pmid: 16470684
references.citation: Development. 2007 Aug;134(15):2771-81
references.pmid: 17596281
references.citation: Development. 1990 Mar;108(3):443-59
references.pmid: 2340809
references.citation: Development. 1996 Nov;122(11):3371-80
references.pmid: 8951054
references.citation: J Physiol. 1988 Sep;403:73-89
references.pmid: 3253426
references.citation: J Exp Biol. 2004 Feb;207(Pt 5):841-52
references.pmid: 14747415
references.citation: J Exp Biol. 2000 Sep;203(Pt 17):2565-79
references.pmid: 10934000
references.citation: Methods Cell Biol. 2004;77:305-29
references.pmid: 15602919
references.citation: J Biol Chem. 2004 Aug 27;279(35):36993-7003
references.pmid: 15213236
references.citation: Development. 2007 Sep;134(17):3145-53
references.pmid: 17670792
references.citation: Nat Rev Genet. 2007 May;8(5):353-67
references.pmid: 17440532
references.citation: Science. 1998 Nov 27;282(5394):1711-4
references.pmid: 9831563
references.citation: Development. 2010 May;137(10):1689-98
references.pmid: 20392743
references.citation: J Neurosci. 2001 Aug 1;21(15):5439-48
references.pmid: 11466415
references.citation: J Cell Biol. 1991 Nov;115(4):1077-89
references.pmid: 1659572
references.citation: Genome Res. 1999 Apr;9(4):334-47
references.pmid: 10207156
references.citation: Genomics. 2006 Feb;87(2):265-74
references.pmid: 16337772
references.citation: Nature. 2007 Mar 1;446(7131):71-5
references.pmid: 17330042
references.citation: J Cell Sci. 2005 Jan 1;118(Pt 1):27-37
references.pmid: 15601660
references.citation: Exp Cell Res. 2005 Jun 10;306(2):336-42
references.pmid: 15925589
references.citation: Curr Opin Cell Biol. 2007 Oct;19(5):521-8
references.pmid: 17945477
references.citation: J Biol Chem. 2011 Jan 7;286(1):806-17
references.pmid: 20843816
references.citation: Brain Res Dev Brain Res. 2001 Aug 23;129(2):169-79
references.pmid: 11506861
references.citation: Cell. 1997 Dec 12;91(6):833-43
references.pmid: 9413992
references.citation: J Neurobiol. 1998 Dec;37(4):622-32
references.pmid: 9858263
references.citation: Cell Commun Adhes. 2003 Jul-Dec;10(4-6):451-6
references.pmid: 14681056
references.citation: Dev Biol. 2011 Jul 15;355(2):194-204
references.pmid: 21554867
references.citation: Dev Genet. 1997;20(2):133-44
references.pmid: 9144924
references.citation: Dev Dyn. 2003 Dec;228(4):709-15
references.pmid: 14648847
references.citation: Nat Genet. 2000 Oct;26(2):216-20
references.pmid: 11017081
references.citation: Proc Natl Acad Sci U S A. 2008 Jan 29;105(4):1255-60
references.pmid: 18202183
references.citation: Dev Neurobiol. 2008 Jan;68(1):45-61
references.pmid: 17918238
references.citation: Dev Neurobiol. 2009 Oct;69(12):780-95
references.pmid: 19634126
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 29;108(13):5425-30
references.pmid: 21383146
references.citation: J Cell Sci. 2004 Oct 15;117(Pt 22):5381-92
references.pmid: 15466892
references.citation: Cardiovasc Res. 2004 May 1;62(2):228-32
references.pmid: 15094343
references.citation: PLoS One. 2010 Jan 01;5(1):e8416
references.pmid: 20049323
references.citation: Nat Rev Mol Cell Biol. 2003 Apr;4(4):285-94
references.pmid: 12671651
references.citation: Cell Tissue Res. 2005 May;320(2):299-310
references.pmid: 15778849