Sealing Holes in Cellular Membranes

Overview

Journal EMBO J

Specialties Biotechnology
Molecular Biology

Date 2021 Mar 1

PMID 33644904

Citations 52

Authors

Yan Zhen

Maja Radulovic

Marina Vietri

Harald Stenmark

Affiliations

Soon will be listed here.

Abstract

The compartmentalization of eukaryotic cells, which is essential for their viability and functions, is ensured by single or double bilayer membranes that separate the cell from the exterior and form boundaries between the cell's organelles and the cytosol. Nascent nuclear envelopes and autophagosomes, which both are enveloped by double membranes, need to be sealed during the late stage of their biogenesis. On the other hand, the integrity of cellular membranes such as the plasma membrane, lysosomes and the nuclear envelope can be compromised by pathogens, chemicals, radiation, inflammatory responses and mechanical stress. There are cellular programmes that restore membrane integrity after injury. Here, we review cellular mechanisms that have evolved to maintain membrane integrity during organelle biogenesis and after injury, including membrane scission mediated by the endosomal sorting complex required for transport (ESCRT), vesicle patching and endocytosis.

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References

Takahashi Y, He H, Tang Z, Hattori T, Liu Y, Young M . An autophagy assay reveals the ESCRT-III component CHMP2A as a regulator of phagophore closure. Nat Commun. 2018; 9(1):2855. PMC: 6054611. DOI: 10.1038/s41467-018-05254-w. View

Olmos Y, Perdrix-Rosell A, Carlton J . Membrane Binding by CHMP7 Coordinates ESCRT-III-Dependent Nuclear Envelope Reformation. Curr Biol. 2016; 26(19):2635-2641. PMC: 5069351. DOI: 10.1016/j.cub.2016.07.039. View

Webster B, Thaller D, Jager J, Ochmann S, Borah S, Lusk C . Chm7 and Heh1 collaborate to link nuclear pore complex quality control with nuclear envelope sealing. EMBO J. 2016; 35(22):2447-2467. PMC: 5109239. DOI: 10.15252/embj.201694574. View

Kass G, Orrenius S . Calcium signaling and cytotoxicity. Environ Health Perspect. 1999; 107 Suppl 1:25-35. PMC: 1566353. DOI: 10.1289/ehp.99107s125. View

Bohannon K, Hanson P . ESCRT puts its thumb on the nanoscale: Fixing tiny holes in endolysosomes. Curr Opin Cell Biol. 2020; 65:122-130. PMC: 7578027. DOI: 10.1016/j.ceb.2020.06.002. View

Chi Y, Chen Z, Jeang K . The nuclear envelopathies and human diseases. J Biomed Sci. 2009; 16:96. PMC: 2770040. DOI: 10.1186/1423-0127-16-96. View

Denais C, Gilbert R, Isermann P, McGregor A, Te Lindert M, Weigelin B . Nuclear envelope rupture and repair during cancer cell migration. Science. 2016; 352(6283):353-8. PMC: 4833568. DOI: 10.1126/science.aad7297. View

Weng I, Chen H, Lo T, Lin W, Chen H, Hsu D . Cytosolic galectin-3 and -8 regulate antibacterial autophagy through differential recognition of host glycans on damaged phagosomes. Glycobiology. 2018; 28(6):392-405. DOI: 10.1093/glycob/cwy017. View

Maciejowski J, Li Y, Bosco N, Campbell P, de Lange T . Chromothripsis and Kataegis Induced by Telomere Crisis. Cell. 2015; 163(7):1641-54. PMC: 4687025. DOI: 10.1016/j.cell.2015.11.054. View

10.

Pieper G, Sprenger S, Teis D, Oliferenko S . ESCRT-III/Vps4 Controls Heterochromatin-Nuclear Envelope Attachments. Dev Cell. 2020; 53(1):27-41.e6. PMC: 7139201. DOI: 10.1016/j.devcel.2020.01.028. View

11.

Vietri M, Radulovic M, Stenmark H . The many functions of ESCRTs. Nat Rev Mol Cell Biol. 2019; 21(1):25-42. DOI: 10.1038/s41580-019-0177-4. View

12.

Lenhart K, ONeill 4th T, Cheng Z, Dee R, Demonbreun A, Li J . GRAF1 deficiency blunts sarcolemmal injury repair and exacerbates cardiac and skeletal muscle pathology in dystrophin-deficient mice. Skelet Muscle. 2015; 5:27. PMC: 4546166. DOI: 10.1186/s13395-015-0054-6. View

13.

Cardenas A, Gonzalez-Jamett A, Cea L, Bevilacqua J, Caviedes P . Dysferlin function in skeletal muscle: Possible pathological mechanisms and therapeutical targets in dysferlinopathies. Exp Neurol. 2016; 283(Pt A):246-54. DOI: 10.1016/j.expneurol.2016.06.026. View

14.

Halfmann C, Sears R, Katiyar A, Busselman B, Aman L, Zhang Q . Repair of nuclear ruptures requires barrier-to-autointegration factor. J Cell Biol. 2019; 218(7):2136-2149. PMC: 6605789. DOI: 10.1083/jcb.201901116. View

15.

Mizushima N, Yoshimori T, Ohsumi Y . The role of Atg proteins in autophagosome formation. Annu Rev Cell Dev Biol. 2011; 27:107-32. DOI: 10.1146/annurev-cellbio-092910-154005. View

16.

Filimonenko M, Stuffers S, Raiborg C, Yamamoto A, Malerod L, Fisher E . Functional multivesicular bodies are required for autophagic clearance of protein aggregates associated with neurodegenerative disease. J Cell Biol. 2007; 179(3):485-500. PMC: 2064794. DOI: 10.1083/jcb.200702115. View

17.

Etxaniz A, Gonzalez-Bullon D, Martin C, Ostolaza H . Membrane Repair Mechanisms against Permeabilization by Pore-Forming Toxins. Toxins (Basel). 2018; 10(6). PMC: 6024578. DOI: 10.3390/toxins10060234. View

18.

Penfield L, Wysolmerski B, Mauro M, Farhadifar R, Martinez M, Biggs R . Dynein pulling forces counteract lamin-mediated nuclear stability during nuclear envelope repair. Mol Biol Cell. 2018; 29(7):852-868. PMC: 5905298. DOI: 10.1091/mbc.E17-06-0374. View

19.

Vargas J, Hatch E, Anderson D, Hetzer M . Transient nuclear envelope rupturing during interphase in human cancer cells. Nucleus. 2012; 3(1):88-100. PMC: 3342953. DOI: 10.4161/nucl.18954. View

20.

Andrews N, Almeida P, Corrotte M . Damage control: cellular mechanisms of plasma membrane repair. Trends Cell Biol. 2014; 24(12):734-42. PMC: 4252702. DOI: 10.1016/j.tcb.2014.07.008. View