title: Association of CHMP4B and autophagy with micronuclei: implications for cataract formation.
abstract: Autophagy is a mechanism of cellular self-degradation that is very important for cellular homeostasis and differentiation. Components of the endosomal sorting complex required for transport (ESCRT) machinery are required for endosomal sorting and also for autophagy and the completion of cytokinesis. Here we show that the ESCRT-III subunit CHMP4B not only localizes to normal cytokinetic bridges but also to chromosome bridges and micronuclei, the latter surrounded by lysosomes and autophagosomes. Moreover, CHMP4B can be co-immunoprecipitated with chromatin. Interestingly, a CHMP4B mutation associated with autosomal dominant posterior polar cataract abolishes the ability of CHMP4B to localize to micronuclei. We propose that CHMP4B, through its association with chromatin, may participate in the autophagolysosomal degradation of micronuclei and other extranuclear chromatin. This may have implications for DNA degradation during lens cell differentiation, thus potentially protecting lens cells from cataract development.
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, 0310 Oslo, Norway ; Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310 Oslo, Norway ; Division of Biomedical Cell Biology, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Antonia P
authors.initials: AP
authors.lastname: Sagona
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, 0310 Oslo, Norway ; Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310 Oslo, Norway ; School of Life Sciences, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Ioannis P
authors.initials: IP
authors.lastname: Nezis
authors.affiliation: Centre for Cancer Biomedicine, Faculty of Medicine, University of Oslo, Montebello, 0310 Oslo, Norway ; Department of Biochemistry, Institute for Cancer Research, Oslo University Hospital, Montebello, 0310 Oslo, Norway.
authors.forename: Harald
authors.initials: H
authors.lastname: Stenmark
mesh_terms: D000818:Animals; D001343:Autophagy; D002386:Cataract / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D056827:Endosomal Sorting Complexes Required for Transport / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D051379:Mice; D048629:Micronuclei, Chromosome-Defective; D041681:NIH 3T3 Cells
chemical_list: C478397:CHMP4B protein, human; D056827:Endosomal Sorting Complexes Required for Transport
references.citation: Autophagy. 2010 Aug;6(6):798-9
references.pmid: 20562532
references.citation: Biochem Biophys Res Commun. 2006 Jan 13;339(2):485-9
references.pmid: 16300732
references.citation: Cell. 2009 Feb 6;136(3):473-84
references.pmid: 19203582
references.citation: Nature. 2009 Oct 1;461(7264):654-8
references.pmid: 19794493
references.citation: Invest Ophthalmol Vis Sci. 2008 Dec;49(12):5466-75
references.pmid: 18676626
references.citation: Exp Eye Res. 1991 Jun;52(6):647-59
references.pmid: 1855541
references.citation: Science. 2011 Mar 25;331(6024):1616-20
references.pmid: 21310966
references.citation: Am J Hum Genet. 2007 Sep;81(3):596-606
references.pmid: 17701905
references.citation: Mutagenesis. 2011 Jan;26(1):125-32
references.pmid: 21164193
references.citation: Nature. 2003 Aug 28;424(6952):1071-4
references.pmid: 12944971
references.citation: Mol Vis. 2012;18:1773-86
references.pmid: 22815631
references.citation: J Biol Chem. 2013 Dec 13;288(50):35626-35
references.pmid: 24142690
references.citation: Cell. 2011 Sep 2;146(5):682-95
references.pmid: 21884931
references.citation: J Biol Chem. 2013 Apr 19;288(16):11436-47
references.pmid: 23479732
references.citation: Nat Cell Biol. 2010 Apr;12(4):362-71
references.pmid: 20208530
references.citation: Adv Immunol. 2011;110:139-61
references.pmid: 21762818
references.citation: J Cell Biol. 2007 Nov 5;179(3):485-500
references.pmid: 17984323
references.citation: J Cell Biol. 2008 Jan 28;180(2):389-402
references.pmid: 18209100
references.citation: Proc Natl Acad Sci U S A. 2011 Mar 22;108(12):4846-51
references.pmid: 21383202
references.citation: Mutat Res. 2003 Jan 10;534(1-2):65-75
references.pmid: 12504755
references.citation: Nat Rev Mol Cell Biol. 2010 Aug;11(8):556-66
references.pmid: 20588296
references.citation: J Cell Sci. 2011 Oct 1;124(Pt 19):3199-207
references.pmid: 21940792
references.citation: FEBS Lett. 2011 Oct 20;585(20):3191-6
references.pmid: 21924267
references.citation: Cell Cycle. 2012 Jan 1;11(1):170-6
references.pmid: 22185757
references.citation: Nature. 2009 Mar 26;458(7237):445-52
references.pmid: 19325624
references.citation: Proc Natl Acad Sci U S A. 2000 May 9;97(10):5357-62
references.pmid: 10805796
references.citation: Nat Cell Biol. 2010 Sep;12(9):814-22
references.pmid: 20811353
references.citation: Chromosoma. 2004 Jun;112(8):389-97
references.pmid: 15156327
references.citation: Am J Hum Genet. 2011 Jun 10;88(6):827-838
references.pmid: 21636066
references.citation: Mol Biol Cell. 2003 Sep;14(9):3821-33
references.pmid: 12972566
references.citation: FEBS J. 2007 Jun;274(12):3055-64
references.pmid: 17509075
references.citation: Exp Eye Res. 2013 Nov;116:141-50
references.pmid: 24012988