Calnexin deficiency leads to dysmyelination.
Calnexin is a molecular chaperone and a component of the quality control of the secretory pathway. We have generated calnexin gene-deficient mice (cnx(-/-)) and showed that calnexin deficiency leads to myelinopathy. Calnexin-deficient mice were viable with no discernible effects on other systems, including immune function, and instead they demonstrated dysmyelination as documented by reduced conductive velocity of nerve fibers and electron microscopy analysis of sciatic nerve and spinal cord. Myelin of the peripheral and central nervous systems of cnx(-/-) mice was disorganized and decompacted. There were no abnormalities in neuronal growth, no loss of neuronal fibers, and no change in fictive locomotor pattern in the absence of calnexin. This work reveals a previously unrecognized and important function of calnexin in myelination and provides new insights into the mechanisms responsible for myelin diseases.
Kraus
Allison
A
Department of Biochemistry, School of Molecular and Systems Medicine, University of Alberta, Edmonton, Alberta T6G 2H7, Canada.
Groenendyk
Jody
J
Bedard
Karen
K
Baldwin
Troy A
TA
Krause
Karl-Heinz
KH
Dubois-Dauphin
Michel
M
Dyck
Jason
J
Rosenbaum
Erica E
EE
Korngut
Lawrence
L
Colley
Nansi J
NJ
Gosgnach
Simon
S
Zochodne
Douglas
D
Todd
Kathryn
K
Agellon
Luis B
LB
Michalak
Marek
M
D000818:Animals; D000831:Animals, Newborn; D037281:Calnexin / Q000235:genetics* / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D003711:Demyelinating Diseases / Q000378:metabolism*; D004594:Electrophysiology / Q000379:methods; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009186:Myelin Sheath / Q000378:metabolism*; D017510:Protein Folding; D012584:Sciatic Nerve / Q000378:metabolism / Q000648:ultrastructure; D013116:Spinal Cord / Q000378:metabolism / Q000648:ultrastructure
D037281:Calnexin
EMBO J. 1995 Jul 17;14(14):3425-33
7628443
J Clin Invest. 2001 May;107(10):1245-53
11375414
Mol Cell Biol. 2002 Nov;22(21):7398-404
12370287
Curr Opin Cell Biol. 2008 Dec;20(6):624-31
18926908
J Biol Chem. 1996 Apr 19;271(16):9332-9
8621597
Proc Natl Acad Sci U S A. 1998 Jan 6;95(1):340-5
9419377
Proc Natl Acad Sci U S A. 2002 Jul 23;99(15):9852-7
12119418
EMBO J. 2001 Dec 3;20(23):6772-82
11726513
J Biol Chem. 1998 Sep 11;273(37):23674-80
9726972
J Biol Chem. 2006 Jan 27;281(4):2338-46
16291754
J Neurochem. 2007 Mar;100(6):1431-48
17241126
Anal Biochem. 1976 May 7;72:248-54
942051
Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):3070-4
7708777
J Cereb Blood Flow Metab. 2005 Mar;25(3):314-24
15647741
Microbiology (Reading). 2004 Sep;150(Pt 9):2825-2835
15347742
J Cell Biol. 1999 Mar 8;144(5):857-68
10085286
EMBO J. 1995 Jul 3;14(13):3064-72
7621821
J Neurosci. 2003 Jul 9;23(14):6152-60
12853434
Nature. 2006 Mar 9;440(7081):215-9
16525473
Neuron. 2001 Sep 27;31(6):957-71
11580896
Biochem J. 2009 Feb 1;417(3):651-66
19133842
Neuron. 2006 Jan 19;49(2):229-41
16423697
BMC Dev Biol. 2006 Nov 19;6:54
17112388
Biochemistry. 1984 Dec 18;23(26):6544-9
6529569
Neuroscience. 2008 Jun 23;154(2):767-83
18456410
Proteomics. 2006 Feb;6(4):1329-39
16404716
Mol Vis. 2008;14:2466-74
19116670
Science. 2002 Feb 22;295(5559):1536-9
11799202
Physiol Rev. 2007 Oct;87(4):1377-408
17928587
Glia. 2006 Sep;54(4):243-57
16856148