Glucosidase II and N-glycan mannose content regulate the half-lives of monoglucosylated species in vivo
Glucosidase II (GII) sequentially removes the two innermost glucose residues from the glycan (Glc3Man9GlcNAc2) transferred to proteins. GII also participates in cycles involving the lectin/chaperones calnexin (CNX) and calreticulin (CRT) as it removes the single glucose unit added to folding interme...
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todo:paper_10591524_v22_n11_p1810_Stigliano2023-10-03T16:01:02Z Glucosidase II and N-glycan mannose content regulate the half-lives of monoglucosylated species in vivo Stigliano, I.D. Alculumbre, S.G. Labriola, C.A. Parodi, A.J. D'Alessio, C. alpha glucosidase ab alpha mannosidase calnexin calreticulin glucosidase II alpha glucosidase IIbeta glycan glycan derivative glycoprotein mannose n glycan mannose unclassified drug amino terminal sequence article endoplasmic reticulum enzyme activity glycosylation nonhuman priority journal protein expression protein folding protein interaction Schizosaccharomyces pombe alpha-Glucosidases alpha-Mannosidase Carbohydrate Sequence Endoplasmic Reticulum Gene Knockout Techniques Glucosyltransferases Glycoproteins Half-Life Hexosyltransferases Mannose Molecular Sequence Data Polysaccharides Protein Folding Protein Interaction Domains and Motifs Protein Stability Protein Structure, Tertiary Schizosaccharomyces Protista Schizosaccharomyces pombe Glucosidase II (GII) sequentially removes the two innermost glucose residues from the glycan (Glc3Man9GlcNAc2) transferred to proteins. GII also participates in cycles involving the lectin/chaperones calnexin (CNX) and calreticulin (CRT) as it removes the single glucose unit added to folding intermediates and misfolded glycoproteins by the UDPGlc: glycoprotein glucosyltransferase (UGGT). GII is a heterodimer in which the á subunit (GIIα) bears the active site, and the β subunit (GIIβ) modulates GIIα activity through its C-terminal mannose 6-phosphate receptor homologous (MRH) domain. Here we report that, as already described in cell-free assays, in live Schizosaccharomyces pombe cells a decrease in the number of mannoses in the glycan results in decreased GII activity. Contrary to previously reported cell-free experiments, however, no such effect was observed in vivo for UGGT. We propose that endoplasmic reticulum α-mannosidase-mediated N-glycan demannosylation of misfolded/slow-folding glycoproteins may favor their interaction with the lectin/chaperone CNX present in S. pombe by prolonging the half-lives of the monoglucosylated glycans (S. pombe lacks CRT). Moreover, we show that even N-glycans bearing five mannoses may interact in vivo with the GIIβ MRH domain and that the N-terminal GIIβ G2B domain is involved in the GIIα-GIIβ interaction. Finally, we report that protists that transfer glycans with low mannose content to proteins have nevertheless conserved the possibility of displaying relatively long-lived monoglucosylated glycans by expressing GIIβ MRH domains with a higher specificity for glycans with high mannose content. © 2011 Stigliano et al. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_10591524_v22_n11_p1810_Stigliano |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
alpha glucosidase ab alpha mannosidase calnexin calreticulin glucosidase II alpha glucosidase IIbeta glycan glycan derivative glycoprotein mannose n glycan mannose unclassified drug amino terminal sequence article endoplasmic reticulum enzyme activity glycosylation nonhuman priority journal protein expression protein folding protein interaction Schizosaccharomyces pombe alpha-Glucosidases alpha-Mannosidase Carbohydrate Sequence Endoplasmic Reticulum Gene Knockout Techniques Glucosyltransferases Glycoproteins Half-Life Hexosyltransferases Mannose Molecular Sequence Data Polysaccharides Protein Folding Protein Interaction Domains and Motifs Protein Stability Protein Structure, Tertiary Schizosaccharomyces Protista Schizosaccharomyces pombe |
| spellingShingle |
alpha glucosidase ab alpha mannosidase calnexin calreticulin glucosidase II alpha glucosidase IIbeta glycan glycan derivative glycoprotein mannose n glycan mannose unclassified drug amino terminal sequence article endoplasmic reticulum enzyme activity glycosylation nonhuman priority journal protein expression protein folding protein interaction Schizosaccharomyces pombe alpha-Glucosidases alpha-Mannosidase Carbohydrate Sequence Endoplasmic Reticulum Gene Knockout Techniques Glucosyltransferases Glycoproteins Half-Life Hexosyltransferases Mannose Molecular Sequence Data Polysaccharides Protein Folding Protein Interaction Domains and Motifs Protein Stability Protein Structure, Tertiary Schizosaccharomyces Protista Schizosaccharomyces pombe Stigliano, I.D. Alculumbre, S.G. Labriola, C.A. Parodi, A.J. D'Alessio, C. Glucosidase II and N-glycan mannose content regulate the half-lives of monoglucosylated species in vivo |
| topic_facet |
alpha glucosidase ab alpha mannosidase calnexin calreticulin glucosidase II alpha glucosidase IIbeta glycan glycan derivative glycoprotein mannose n glycan mannose unclassified drug amino terminal sequence article endoplasmic reticulum enzyme activity glycosylation nonhuman priority journal protein expression protein folding protein interaction Schizosaccharomyces pombe alpha-Glucosidases alpha-Mannosidase Carbohydrate Sequence Endoplasmic Reticulum Gene Knockout Techniques Glucosyltransferases Glycoproteins Half-Life Hexosyltransferases Mannose Molecular Sequence Data Polysaccharides Protein Folding Protein Interaction Domains and Motifs Protein Stability Protein Structure, Tertiary Schizosaccharomyces Protista Schizosaccharomyces pombe |
| description |
Glucosidase II (GII) sequentially removes the two innermost glucose residues from the glycan (Glc3Man9GlcNAc2) transferred to proteins. GII also participates in cycles involving the lectin/chaperones calnexin (CNX) and calreticulin (CRT) as it removes the single glucose unit added to folding intermediates and misfolded glycoproteins by the UDPGlc: glycoprotein glucosyltransferase (UGGT). GII is a heterodimer in which the á subunit (GIIα) bears the active site, and the β subunit (GIIβ) modulates GIIα activity through its C-terminal mannose 6-phosphate receptor homologous (MRH) domain. Here we report that, as already described in cell-free assays, in live Schizosaccharomyces pombe cells a decrease in the number of mannoses in the glycan results in decreased GII activity. Contrary to previously reported cell-free experiments, however, no such effect was observed in vivo for UGGT. We propose that endoplasmic reticulum α-mannosidase-mediated N-glycan demannosylation of misfolded/slow-folding glycoproteins may favor their interaction with the lectin/chaperone CNX present in S. pombe by prolonging the half-lives of the monoglucosylated glycans (S. pombe lacks CRT). Moreover, we show that even N-glycans bearing five mannoses may interact in vivo with the GIIβ MRH domain and that the N-terminal GIIβ G2B domain is involved in the GIIα-GIIβ interaction. Finally, we report that protists that transfer glycans with low mannose content to proteins have nevertheless conserved the possibility of displaying relatively long-lived monoglucosylated glycans by expressing GIIβ MRH domains with a higher specificity for glycans with high mannose content. © 2011 Stigliano et al. |
| format |
JOUR |
| author |
Stigliano, I.D. Alculumbre, S.G. Labriola, C.A. Parodi, A.J. D'Alessio, C. |
| author_facet |
Stigliano, I.D. Alculumbre, S.G. Labriola, C.A. Parodi, A.J. D'Alessio, C. |
| author_sort |
Stigliano, I.D. |
| title |
Glucosidase II and N-glycan mannose content regulate the half-lives of monoglucosylated species in vivo |
| title_short |
Glucosidase II and N-glycan mannose content regulate the half-lives of monoglucosylated species in vivo |
| title_full |
Glucosidase II and N-glycan mannose content regulate the half-lives of monoglucosylated species in vivo |
| title_fullStr |
Glucosidase II and N-glycan mannose content regulate the half-lives of monoglucosylated species in vivo |
| title_full_unstemmed |
Glucosidase II and N-glycan mannose content regulate the half-lives of monoglucosylated species in vivo |
| title_sort |
glucosidase ii and n-glycan mannose content regulate the half-lives of monoglucosylated species in vivo |
| url |
http://hdl.handle.net/20.500.12110/paper_10591524_v22_n11_p1810_Stigliano |
| work_keys_str_mv |
AT stiglianoid glucosidaseiiandnglycanmannosecontentregulatethehalflivesofmonoglucosylatedspeciesinvivo AT alculumbresg glucosidaseiiandnglycanmannosecontentregulatethehalflivesofmonoglucosylatedspeciesinvivo AT labriolaca glucosidaseiiandnglycanmannosecontentregulatethehalflivesofmonoglucosylatedspeciesinvivo AT parodiaj glucosidaseiiandnglycanmannosecontentregulatethehalflivesofmonoglucosylatedspeciesinvivo AT dalessioc glucosidaseiiandnglycanmannosecontentregulatethehalflivesofmonoglucosylatedspeciesinvivo |
| _version_ |
1782026509659144192 |