Functional characterization of two secreted SEL1L isoforms capable of exporting unassembled substrate
Articolo
Data di Pubblicazione:
2009
Citazione:
Functional characterization of two secreted SEL1L isoforms capable of exporting unassembled substrate / M. Cattaneo, L.V. Lotti, S. Martino, M. Cardano, R. Orlandi, R. Mariani-Costantini, I. Biunno. - In: THE JOURNAL OF BIOLOGICAL CHEMISTRY. - ISSN 0021-9258. - 284:17(2009 Apr 24), pp. 11405-11415.
Abstract:
SEL1L-A, a transmembrane glycoprotein residing in the endoplasmic reticulum (ER), is a component of the ER-associated degradation (ERAD) pathway. Alternative splicing generates two smaller SEL1L isoforms, -B and -C, that lack the SEL1L-A membrane-spanning region but retainsomesel-1-like repeats,known to be involved in multi-protein interactions and signal transduction.
In this study the functional characteristics of SEL1L-B and -C were investigated in human cell models. We show that these two isoforms
are induced upon ER stress and activation of the unfolded protein response, together withSEL1L-A.Using transient transfection
experiments (based on wild-type and mutant SEL1L constructs) combined with several biochemical tests we show that SEL1L-B and, more prominently, SEL1L-C are secreted glycoproteins. Although SEL1L-C is in monomeric form, SEL1L-B is engaged in intramolecular/intermolecular disulfide bonds. Both isoforms localize in secretory and degradative cellular compartments
and in areas of cell-cell contact. However, whereas SEL1L-B is mainly associated with membranes, SEL1L-C shows the typical
intralumenal localization of soluble proteins and is present in intercellular spaces. Furthermore, because of its peroxisomal domain, SEL1L-C localizes to peroxisomes. Both SEL1L-B and -C are involved in sorting and exporting unassembled Ig- s but do not affect two other ERAD substrates, the null Hong Kong variant of 1-antitrypsin, and mutant 1-AT Z. Overall these findings suggest that SEL1L-B and -C participate to novel molecular
pathways that, in parallel with ERAD, contribute to the disposure of misfolded/unfolded or orphan proteins through degradation or secretion.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
pancreas-specific gene ; endoplasmic-reticulum ; hepatocellular-carcinoma ; protein ; expression ; identification ; proteasome ; autophagy ; antibody ; region
Elenco autori:
M. Cattaneo, L.V. Lotti, S. Martino, M. Cardano, R. Orlandi, R. Mariani-Costantini, I. Biunno
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