NET37, a nuclear envelope transmembrane protein with glycosidase homology, is involved in myoblast differentiation.
The nuclear lamina and its associated proteins are important for nuclear structure and chromatin organization and also have been implicated in the regulation of cell signaling and gene expression. In this study we demonstrate that the lamina-associated nuclear envelope transmembrane protein NET37 is required for myogenic differentiation of C2C12 cells. NET37, a member of glycosidase family 31, is highly expressed in mouse skeletal muscle and is strongly up-regulated during C2C12 differentiation. By protease mapping we show that its glycosidase homology domain is located in the lumen of the nuclear envelope/endoplasmic reticulum. When NET37 is depleted from proliferating myoblasts by RNAi, myogenic differentiation is significantly impaired, and there is a concomitant delay in up-regulation of the late myogenic transcription factor myogenin. We expressed silencing-resistant NET37 mutated at a conserved residue in the glycosidase domain and found that this predicted catalytically inactive protein is unable to support myogenesis in cells depleted of wild type NET37. Therefore, the enzymatic function of NET37 appears to be important for myogenic differentiation. C2C12 cells depleted of NET37 have reduced activation of Akt after shifting to differentiation medium and are defective in insulin like growth factor-II (IGF-II) secretion, an autocrine/paracrine factor involved in Akt activation. We also observed that pro-IGF-II co-immunoprecipitates with NET37. Based on our results, we propose that NET37 has a role in IGF-II maturation in the secretory pathway during myoblast differentiation. The localization of NET37 at the nuclear envelope raises the possibility that it may coordinate myogenic events between the nuclear interior and the endoplasmic reticulum lumen via transmembrane communication.
Datta
Kaustuv
K
Department of Cell Biology and Molecular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
Guan
Tinglu
T
Gerace
Larry
L
D000818:Animals; D019898:Autocrine Communication / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology*; D002460:Cell Line; D006026:Glycoside Hydrolases; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D018008:Myogenin / Q000096:biosynthesis / Q000235:genetics; D009685:Nuclear Envelope / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D019899:Paracrine Communication / Q000502:physiology; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic / Q000502:physiology
C503801:Myog protein, mouse; D018008:Myogenin; D009687:Nuclear Proteins; D007335:Insulin-Like Growth Factor II; D051057:Proto-Oncogene Proteins c-akt; D006026:Glycoside Hydrolases
Am J Hum Genet. 2003 Apr;72(4):1013-7
12618959
J Cell Biol. 2008 Sep 8;182(5):979-91
18762576
Genes Dev. 2006 Feb 15;20(4):486-500
16481476
Curr Opin Struct Biol. 1997 Oct;7(5):637-44
9345621
EMBO J. 2008 Jan 23;27(2):315-27
18216874
Mol Cell Biol. 2000 Dec;20(23):8983-95
11073997
J Am Chem Soc. 2002 May 8;124(18):4948-9
11982345
Eur J Biochem. 2001 Apr;268(8):2270-80
11298744
J Biol Chem. 2003 Oct 17;278(42):41109-13
12941952
J Clin Invest. 2007 May;117(5):1282-93
17446932
Mol Cell Biol. 2007 May;27(10):3716-31
17353260
N Engl J Med. 1999 Dec 2;341(23):1715-24
10580070
Genes Dev. 2007 May 1;21(9):1125-38
17473174
BMC Cell Biol. 2006 Oct 24;7:38
17062158
J Biol Chem. 1997 Jan 10;272(2):791-7
8995365
J Biol Chem. 1998 Jul 17;273(29):18443-51
9660813
Nat Rev Mol Cell Biol. 2005 Jan;6(1):21-31
15688064
Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1206-10
14745025
Glycobiology. 2003 Sep;13(9):77R-91R
12736198
Annu Rev Physiol. 1991;53:201-16
2042960
J Biol Chem. 2000 Feb 18;275(7):4840-7
10671519
J Cell Biol. 2003 Dec 8;163(5):931-6
14662739
Biochem J. 2001 Oct 15;359(Pt 2):381-6
11583585
J Cell Sci. 2002 Sep 15;115(Pt 18):3587-99
12186945
Cell. 2003 Jun 13;113(6):685-700
12809600
J Biol Chem. 1979 Sep 25;254(18):8814-8
479161
Biochem Soc Trans. 2008 Dec;36(Pt 6):1329-34
19021550
Curr Opin Genet Dev. 2003 Jun;13(3):223-30
12787783
J Biol Chem. 2005 Apr 22;280(16):15992-6001
15647271
Int Rev Cytol. 2007;261:1-46
17560279
Biochem J. 1995 Oct 1;311 ( Pt 1):350-1
7575477
FEBS J. 2007 Mar;274(6):1383-92
17489096
J Bacteriol. 1994 May;176(10):2828-34
8188584
Mol Biol Cell. 2009 Mar;20(6):1855-64
19158397
Nat Genet. 2004 Nov;36(11):1213-8
15489854
Int Rev Cytol. 2005;246:231-79
16164970
FEBS Lett. 2008 Jun 18;582(14):2023-32
18474238
Nat Cell Biol. 2001 Nov;3(11):1009-13
11715022
J Biol Chem. 1980 Mar 25;255(6):2255-8
7358666
Mol Cell Biol. 1995 Jul;15(7):3823-9
7791789
Plant Mol Biol. 1998 May;37(1):1-13
9620260
Nat Genet. 2001 Feb;27(2):195-200
11175789
Nat Cell Biol. 2001 Nov;3(11):1014-9
11715023
Physiol Rev. 2004 Jan;84(1):209-38
14715915
Exp Cell Res. 2007 Jun 10;313(10):2121-33
17467691
Hum Mol Genet. 2007 Aug 1;16(15):1884-95
17567779
Nat Genet. 1994 Dec;8(4):323-7
7894480
Mol Cell Biol. 2007 Jul;27(13):4698-707
17452443
Science. 2003 Sep 5;301(5638):1380-2
12958361
J Biol Chem. 2007 Feb 23;282(8):5106-10
17218321
J Cell Biol. 2000 Dec 11;151(6):1131-40
11121430
J Biol Chem. 2006 Oct 6;281(40):29962-71
16901893
J Biol Chem. 1982 Sep 10;257(17):9990-10000
7050114
Science. 2007 Nov 30;318(5855):1408-12
18048680
Nat Genet. 1999 Mar;21(3):285-8
10080180
Trends Cell Biol. 2006 Jan;16(1):36-44
16325404
Hum Mol Genet. 2000 May 22;9(9):1453-9
10814726
Hum Mol Genet. 1996 Jun;5(6):801-8
8776595
Mol Biol Cell. 2004 Feb;15(2):497-505
14595115
Annu Rev Biochem. 1998;67:753-91
9759503
J Biol Chem. 1991 Jul 25;266(21):13507-12
1856189