The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z‐α1‐antitrypsin



Dickens, JA, Ordóñez, A, Chambers, JE, Beckett, AJ ORCID: 0000-0001-8377-325X, Patel, V, Malzer, E, Dominicus, CS, Bradley, J, Peden, AA, Prior, IA ORCID: 0000-0002-4055-5161
et al (show 2 more authors) (2016) The endoplasmic reticulum remains functionally connected by vesicular transport after its fragmentation in cells expressing Z‐α1‐antitrypsin. The FASEB Journal, 30 (12). 4083 - 4097.

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Abstract

Alpha-1-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.

Item Type: Article
Uncontrolled Keywords: ER stress, homotypic fusion, serpin, SNARE
Depositing User: Symplectic Admin
Date Deposited: 26 Sep 2016 14:01
Last Modified: 25 Nov 2021 12:38
DOI: 10.1096/fj.201600430R
Open Access URL: https://www.researchgate.net/publication/307890347
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3003455