UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z-alpha(1)-antitrypsin

Dickens, JA; Ordonez, A; Chambers, JE; Beckett, AJ; Patel, V; Malzer, E; Dominicus, CS; ... Marciniak, SJ; + view all (2016) The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z-alpha(1)-antitrypsin. FASEB Journal , 30 (12) pp. 4083-4097. 10.1096/fj.201600430R. Green open access

[thumbnail of Manzotti_FASEB J-2016-Dickens-4083-97.pdf]
Preview
Text
Manzotti_FASEB J-2016-Dickens-4083-97.pdf - Published Version

Download (3MB) | Preview

Abstract

α1-Antitrypsin is a serine protease inhibitor produced in the liver that is responsible for the regulation of pulmonary inflammation. The commonest pathogenic gene mutation yields Z-α1-antitrypsin, which has a propensity to self-associate forming polymers that become trapped in inclusions of endoplasmic reticulum (ER). It is unclear whether these inclusions are connected to the main ER network in Z-α1-antitrypsin-expressing cells. Using live cell imaging, we found that despite inclusions containing an immobile matrix of polymeric α1-antitrypsin, small ER resident proteins can diffuse freely within them. Inclusions have many features to suggest they represent fragmented ER, and some are physically separated from the tubular ER network, yet we observed cargo to be transported between them in a cytosol-dependent fashion that is sensitive to N-ethylmaleimide and dependent on Sar1 and sec22B. We conclude that protein recycling occurs between ER inclusions despite their physical separation.—Dickens, J. A., Ordóñez, A., Chambers, J. E., Beckett, A. J., Patel, V., Malzer, E., Dominicus, C. S., Bradley, J., Peden, A. A., Prior, I. A., Lomas, D. A., Marciniak, S. J. The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z-α1-antitrypsin.

Type: Article
Title: The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z-alpha(1)-antitrypsin
Open access status: An open access version is available from UCL Discovery
DOI: 10.1096/fj.201600430R
Publisher version: http://dx.doi.org/10.1096/fj.201600430R
Language: English
Additional information: © The Author(s). This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 International (CC BY 4.0) (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biology, Cell Biology, Life Sciences & Biomedicine - Other Topics, Er Stress, Homotypic Fusion, Serpin, Snare, Unfolded Protein Response, Nf-Kappa-B, Alpha(1)-Antitrypsin Deficiency, Mammalian-Cells, Russell Bodies, Er, Alpha-1-Antitrypsin, Accumulation, Polymers, Fusion
UCL classification: UCL
UCL > Provost and Vice Provost Offices > VP: Health
URI: https://discovery.ucl.ac.uk/id/eprint/1517631
Downloads since deposit
24Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item