Modification of a recombinant GPI-anchored metalloproteinase for secretion alters the protein glycosylation

Morrison, Chet A.; Easton, Richard L.; Morris, Howard R.; McMaster, W. Robert; Piret, James M.; Dell, Anne

doi:10.1002/(sici)1097-0290(20000520)68:4<407::aid-bit6>3.0.co;2-s

Cited by 4 publications

(2 citation statements)

References 80 publications

(59 reference statements)

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“…2C), the increase in oligomannose levels is limited to the secretome. This observation highlights the importance of separately evaluating membrane and secreted N-glycans in glycomic experiments, as we have also noted in prior work (29,30).…”

Section: Xbp1s Remodels Hela Xbp1s Membrane N-glycoproteomes In a Cellsupporting

confidence: 80%

XBP1s activation can globally remodel N-glycan structure distribution patterns

Wong

Chen

Antonopoulos

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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Classically, the unfolded protein response (UPR) safeguards secretory pathway proteostasis. The most ancient arm of the UPR, the IRE1-activated spliced X-box binding protein 1 (XBP1s)-mediated response, has roles in secretory pathway maturation beyond resolving proteostatic stress. Understanding the consequences of XBP1s activation for cellular processes is critical for elucidating mechanistic connections between XBP1s and development, immunity, and disease. Here, we show that a key functional output of XBP1s activation is a cell type-dependent shift in the distribution of N-glycan structures on endogenous membrane and secreted proteomes. For example, XBP1s activity decreased levels of sialylation and bisecting GlcNAc in the HEK293 membrane proteome and secretome, while substantially increasing the population of oligomannose N-glycans only in the secretome. In HeLa cell membranes, stress-independent XBP1s activation increased the population of high-mannose and tetraantennary N-glycans, and also enhanced core fucosylation. mRNA profiling experiments suggest that XBP1s-mediated remodeling of the N-glycome is, at least in part, a consequence of coordinated transcriptional resculpting of N-glycan maturation pathways by XBP1s. The discovery of XBP1s-induced N-glycan structural remodeling on a glycome-wide scale suggests that XBP1s can act as a master regulator of N-glycan maturation. Moreover, because the sugars on cell-surface proteins or on proteins secreted from an XBP1s-activated cell can be molecularly distinct from those of an unactivated cell, these findings reveal a potential new mechanism for translating intracellular stress signaling into altered interactions with the extracellular environment.

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Section: Xbp1s Remodels Hela Xbp1s Membrane N-glycoproteomes In a Cellsupporting

confidence: 80%

XBP1s activation can globally remodel N-glycan structure distribution patterns

Wong

Chen

Antonopoulos

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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“…It is noteworthy that the size of 7/11 differs between the secreted and intracellular forms and may reflect different posttranslational processing of the secreted protein. Differences in glycosylation have been observed previously between intracellular/membrane proteins and secreted proteins in CHO-K1 cells (Hooker et al 1999, Morrison et al 2000. Along these lines, the vesiculated intracellular distribution of 7/11 is of interest.…”

mentioning

confidence: 99%

Alternative splicing to exon 11 of human prolactin receptor gene results in multiple isoforms including a secreted prolactin-binding protein

Trott

Hovey

Koduri

et al. 2003

Journal of Molecular Endocrinology

109

135

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Endocrine and autocrine prolactin (PRL) exerts effects on normal breast and breast cancer cells, and high serum PRL is a poor prognostic factor for colorectal cancer. Here we tested the hypothesis that short isoforms of the PRL receptor (PRLR) in human tissue regulate the actions of PRL in cancer. Using 3′ RACE we isolated five splice variants of the human PRLR (hPRLR), three of which encode the complete extracellular binding domain. Two of these isoforms, short form 1a (SF1a) and short form 1b (SF1b), possess unique intracellular domains encoded by splicing to exon 11 from exons 10 and 9 respectively. A third novel isoform (∆7/11) reflects alternative splicing from exon 7 to exon 11 and encodes a secreted soluble PRL-binding protein. Additional splice variants of SF1b and ∆7/11 that lacked exon 4 (∆4-SF1b and ∆4-∆7/11) were also identified. Functional analyses indicated that hPRLR-SF1b is a strong dominant-negative to the differentiative function of the PRLR long form while hPRLR-SF1a is a weaker dominant-negative. Differential abundance of SF1a, SF1b and ∆7/11 expression was detected in normal breast, colon, placenta, kidney, liver, ovary and pancreas, and breast and colon tumors. Taken together, these data indicate the presence of multiple isoforms of the hPRLR that may function to modulate the endocrine and autocrine effects of PRL in normal human tissue and cancer.

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