Transport of protein disulfide isomerase from the endoplasmic reticulum to the extracellular space without passage through the Golgi complex.

Autor:	Oliveira PVS; Division of Genetics and Cell Biology Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy; Laboratorio de Biologia Vascular, LIM-64 (Biologia Cardiovascular Translacional), Instituto do Coração (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil., Dalla Torre M; Division of Genetics and Cell Biology Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy., Debbas V; Laboratorio de Biologia Vascular, LIM-64 (Biologia Cardiovascular Translacional), Instituto do Coração (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil., Orsi A; Division of Genetics and Cell Biology Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy., Laurindo FRM; Laboratorio de Biologia Vascular, LIM-64 (Biologia Cardiovascular Translacional), Instituto do Coração (InCor), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil. Electronic address: francisco.laurindo@hc.fm.usp.br., Sitia R; Division of Genetics and Cell Biology Vita-Salute San Raffaele University and IRCCS San Raffaele Scientific Institute, Milan, Italy. Electronic address: sitia.roberto@hsr.it.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Aug; Vol. 300 (8), pp. 107536. Date of Electronic Publication: 2024 Jul 04.
DOI:	10.1016/j.jbc.2024.107536
Abstrakt:	Protein disulfide isomerase-A1 (PDIA1) is a master regulator of oxidative protein folding and proteostasis in the endoplasmic reticulum (ER). However, PDIA1 can reach the extracellular space, impacting thrombosis and other pathophysiological phenomena. Whether PDIA1 is externalized via passive release or active secretion is not known. To investigate how PDIA1 negotiates its export, we generated a tagged variant that undergoes N-glycosylation in the ER (Glyco-PDIA1). Addition of N-glycans does not alter its enzymatic functions. Upon either deletion of its KDEL ER-localization motif or silencing of KDEL receptors, Glyco-PDIA1 acquires complex glycans in the Golgi and is secreted. In control cells, however, Glyco-PDIA1 is released with endoglycosidase-H sensitive glycans, implying that it does not follow the classical ER-Golgi route nor does it encounter glycanases in the cytosol. Extracellular Glyco-PDIA1 is more abundant than actin, lactate dehydrogenase, or other proteins released by damaged or dead cells, suggesting active transport through a Golgi-independent route. The strategy we describe herein can be extended to dissect how select ER-residents reach the extracellular space. Competing Interests: Conflicts of interest The authors declare no conflict of interest with contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu