A bacterial glycosidase enables mannose-6-phosphate modification and improved cellular uptake of yeast-produced recombinant human lysosomal enzymes

2012 ◽  
Vol 30 (12) ◽  
pp. 1225-1231 ◽  
Author(s):  
Petra Tiels ◽  
Ekaterina Baranova ◽  
Kathleen Piens ◽  
Charlotte De Visscher ◽  
Gwenda Pynaert ◽  
...  
Keyword(s):  
Cellular Uptake ◽  
Lysosomal Enzymes ◽  
Mannose 6 Phosphate

scholarly journals Chemoenzymatic glycan-selective remodeling of a therapeutic lysosomal enzyme with high-affinity M6P-glycan ligands. Enzyme substrate specificity is the name of the game

2021 ◽  
Author(s):  
Xiao Zhang ◽  
Huiying Liu ◽  
Naresh Meena ◽  
Chao Li ◽  
Guanghui Zong ◽  
...  
Keyword(s):  
Substrate Specificity ◽  
Cellular Uptake ◽  
Lysosomal Enzyme ◽  
Therapeutic Efficacy ◽  
Lysosomal Enzymes ◽  
High Affinity ◽  
Enzyme Substrate ◽  
Mannose 6 Phosphate

Functionalization of therapeutic lysosomal enzymes with mannose-6-phosphate (M6P) glycan ligands represents a major strategy for enhancing the cation-independent M6P receptor (CI-MPR)-mediated cellular uptake, thus improving the overall therapeutic efficacy of...

scholarly journals Mannose 6-phosphate receptor dependent secretion of lysosomal enzymes.

1990 ◽  
Vol 9 (11) ◽  
pp. 3507-3513 ◽  
Author(s):  
H. H. Chao ◽  
A. Waheed ◽  
R. Pohlmann ◽  
A. Hille ◽  
K. von Figura
Keyword(s):  
Lysosomal Enzymes ◽  
Mannose 6 Phosphate

Biosynthesis and secretion of the mannose 6-phosphate receptor and its ligands in polarized Caco-2 cells

1999 ◽  
Vol 277 (3) ◽  
pp. G506-G514 ◽  
Author(s):  
Debra A. Wick ◽  
Bellur Seetharam ◽  
Nancy M. Dahms
Keyword(s):  
Lysosomal Enzymes ◽  
Colon Adenocarcinoma ◽  
Brefeldin A ◽  
Human Colon ◽  
Adenocarcinoma Cell Line ◽  
Cell Lysate ◽  
Factor Ii ◽  
Specific Antisera ◽  
Mannose 6 Phosphate ◽  
Human Colon Adenocarcinoma

We have analyzed the transport of newly synthesized mannose 6-phosphate (Man-6- P)-bearing proteins (i.e., lysosomal enzymes) in the polarized human colon adenocarcinoma cell line, Caco-2, by subjecting filter-grown cells to a pulse-chase labeling protocol using [35S]methionine, and the resulting cell lysate, apical medium, and basolateral medium were immunoprecipitated with insulin-like growth factor II/Man-6- P receptor (IGF-II/MPR)-specific antisera. The results showed that the majority of secreted lysosomal enzymes accumulated in the apical medium at >2 h of chase and that this polarized distribution was facilitated by the IGF-II/MPR selectively endocytosing lysosomal enzymes from the basolateral surface. Treatment with various agents known to affect vesicular transport events demonstrated that incubations at 16°C or incubations with brefeldin A inhibited the secretion of lysosomal enzymes from both the apical and basolateral surface, whereas treatment with nocodazole selectively blocked apical secretion. In contrast, incubation with NH4Cl or nocodazole had a stimulatory effect on basolateral secretion. Taken together, these results demonstrate that the sorting of Man-6- P-containing proteins into the apical and basolateral secretory pathways is regulated by distinct components of the intracellular trafficking machinery.

scholarly journals Azurophilic Granules of Human Neutrophilic Leukocytes Are Deficient in Lysosome-Associated Membrane Proteins but Retain the Mannose 6-Phosphate Recognition Marker

Blood ◽  
1998 ◽  
Vol 91 (3) ◽  
pp. 1044-1058 ◽  
Author(s):  
A.-M. Cieutat ◽  
P. Lobel ◽  
J.T. August ◽  
L. Kjeldsen ◽  
H. Sengeløv ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Lysosomal Enzymes ◽  
Acid Hydrolases ◽  
Structural Localization ◽  
Dense Bodies ◽  
Neutrophilic Leukocytes ◽  
Azurophil Granule ◽  
Membrane Bound ◽  
Storage Granules ◽  
Mannose 6 Phosphate

Abstract During granulocyte differentiation in the bone marrow (BM), neutrophilic leukocyte precursors synthesize large amounts of lysosomal enzymes. These enzymes are sequestered into azurophilic storage granules until used days later for digestion of phagocytized microorganisms after leukocyte emigration to inflamed tissues. This azurophil granule population has previously been defined as a primary lysosome, ie, a membrane-bound organelle containing acid hydrolases that have not entered into a digestive event. In this study, azurophil granules were purified and shown to contain large amounts of mannose 6-phosphate-containing glycoproteins (Man 6-P GP) but little lysosome-associated membrane proteins (LAMP). In addition, the fine structural localization of Man 6-P GP and LAMP was investigated at various stages of maturation in human BM and blood. Man 6-P GP were present within the azurophilic granules at all stages of maturation and in typical multivesicular bodies (MVB) as well as in multilaminar compartments (MLC), identified by their content of concentric arrays of internal membranes. LAMP was absent in all identified granule populations, but was consistently found in the membranes of vesicles, MVB, and MLC. The latter compartment has not been previously described in this cell type. In conclusion, the azurophilic granules, which contain an abundance of lysosomal enzymes and Man 6-P GP, lack the LAMP glycoproteins. By current criteria, they therefore cannot be classified as lysosomes, but rather may have the functional characteristics of a regulated secretory granule. Rather, the true lysosomes of the resting neutrophil are probably the MVB and MLC. Finally, the typical “dense bodies” or mature lysosomes described in other cells are not present in resting neutrophils.

Drug-induced phospholipidosis is caused by blockade of mannose 6-phosphate receptor-mediated targeting of lysosomal enzymes

2008 ◽  
Vol 377 (1) ◽  
pp. 268-274 ◽  
Author(s):  
Kazuhiko Ikeda ◽  
Masahiro Hirayama ◽  
Yuko Hirota ◽  
Erika Asa ◽  
Jiro Seki ◽  
...  
Keyword(s):  
Lysosomal Enzymes ◽  
Drug Induced ◽  
Mannose 6 Phosphate
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