Role of cation independent mannose 6-phosphate receptor protein in sorting and intracellular trafficking of lysosomal enzymes in chicken embryonic fibroblast (CEF) cells

2009 ◽  
Vol 27 (1) ◽  
pp. 39-48 ◽  
Author(s):  
Sivaramakrishna Yadavalli ◽  
Siva Kumar Nadimpalli
Keyword(s):  
Intracellular Trafficking ◽  
Lysosomal Enzymes ◽  
Receptor Protein ◽  
Chicken Embryonic Fibroblast ◽  
Mannose 6 Phosphate ◽  
Embryonic Fibroblast

scholarly journals Role of LAMP-2 in Lysosome Biogenesis and Autophagy

2002 ◽  
Vol 13 (9) ◽  
pp. 3355-3368 ◽  
Author(s):  
Eeva-Liisa Eskelinen ◽  
Anna Lena Illert ◽  
Yoshitaka Tanaka ◽  
Günter Schwarzmann ◽  
Judith Blanz ◽  
...  
Keyword(s):  
Half Life ◽  
Lysosomal Enzymes ◽  
State Level ◽  
Autophagic Vacuoles ◽  
Lysosome Biogenesis ◽  
Golgi Region ◽  
Activity Measurements ◽  
Phenotype Analysis ◽  
Mannose 6 Phosphate

In LAMP-2–deficient mice autophagic vacuoles accumulate in many tissues, including liver, pancreas, muscle, and heart. Here we extend the phenotype analysis using cultured hepatocytes. In LAMP-2–deficient hepatocytes the half-life of both early and late autophagic vacuoles was prolonged as evaluated by quantitative electron microscopy. However, an endocytic tracer reached the autophagic vacuoles, indicating delivery of endo/lysosomal constituents to autophagic vacuoles. Enzyme activity measurements showed that the trafficking of some lysosomal enzymes to lysosomes was impaired. Immunoprecipitation of metabolically labeled cathepsin D indicated reduced intracellular retention and processing in the knockout cells. The steady-state level of 300-kDa mannose 6-phosphate receptor was slightly lower in LAMP-2–deficient hepatocytes, whereas that of 46-kDa mannose 6-phosphate receptor was decreased to 30% of controls due to a shorter half-life. Less receptor was found in the Golgi region and in vesicles and tubules surrounding multivesicular endosomes, suggesting impaired recycling from endosomes to the Golgi. More receptor was found in autophagic vacuoles, which may explain its shorter half-life. Our data indicate that in hepatocytes LAMP-2 deficiency either directly or indirectly leads to impaired recycling of 46-kDa mannose 6-phosphate receptors and partial mistargeting of a subset of lysosomal enzymes. Autophagic vacuoles may accumulate due to impaired capacity for lysosomal degradation.

scholarly journals Studies of the biosynthesis of the mannose 6-phosphate receptor in receptor-positive and -deficient cell lines.

1983 ◽  
Vol 97 (6) ◽  
pp. 1700-1706 ◽  
Author(s):  
D E Goldberg ◽  
C A Gabel ◽  
S Kornfeld
Keyword(s):  
Cell Lines ◽  
Lysosomal Enzymes ◽  
Cell Types ◽  
Receptor Protein ◽  
Complex Type ◽  
Cultured Cell ◽  
Selective Targeting ◽  
High Mannose ◽  
Mannose 6 Phosphate ◽  
Intracellular Pathway

Phosphomannosyl residues present on lysosomal enzymes are specifically recognized by the mannose 6-phosphate receptor protein. This interaction results in the selective targeting of lysosomal enzymes to lysosomes. While this pathway is operative in many cell types, we have found four cultured cell lines that are deficient in the ability to bind lysosomal enzymes containing phosphomannosyl residues to their intracellular or surface membranes (Gabel, C., D. Goldberg, and S. Kornfeld, 1983, Proc. Natl. Acad. Sci. USA, 80:775-779). These cells appear to segregate lysosomal enzymes by an alternate intracellular pathway. To determine the basis for the lack of mannose 6-phosphate receptor activity in these cell lines, we studied the biosynthesis of the receptor in receptor-positive (BW5147) and receptor-deficient (P388D1 and MOPC 315) cells. The cells were labeled with [2-3H]mannose or [35S]methionine and the receptor was immunoprecipitated with an antireceptor antiserum. BW5147 cells synthesize a receptor protein whose size increases after translation/glycosylation. MOPC 315 cells produce an apparently normal receptor and degrade it rapidly. P388D1 cells fail to synthesize any detectable receptor. The receptor from BW5147 and MOPC 315 cells is a glycoprotein with both high mannose and complex asparagine-linked oligosaccharides. The complex-type units become fully sialylated and remain so during long periods of chase.

Identification of the Putative Mannose 6-phosphate Receptor Protein (MPR 300) in the Invertebrate unio

1999 ◽  
Vol 19 (5) ◽  
pp. 403-409 ◽  
Author(s):  
Yerramalla Udaya Lakshmi ◽  
Yalamarthy Radha ◽  
Annette Hille-Rehfeld ◽  
Kurt von Figura ◽  
Nadimpalli Siva Kumar
Keyword(s):  
Affinity Chromatography ◽  
Lysosomal Enzymes ◽  
Receptor Protein ◽  
Immunological Properties ◽  
Receptor Proteins ◽  
Mannose 6 Phosphate ◽  
Mpr 46

In mammals, Mannose 6-phosphate receptor proteins (MPR 300 and MPR 46) mediate transport of lysosomal enzymes to lysosomes. Both receptors have been found in non-mammalian vertebrates including fish. To investigate the presence of MPRs in invertebrates, MPR 300 protein was isolated from the mollusc unio by affinity chromatography. It was shown to exhibit biochemical and immunological properties similar to mammalian MPR 300.

THE ROLE OF LYSOSOMAL ENZYMES IN THE PATHOGENESIS OF SHOCK. 2, THE ORIGIN OF PLASMA LYSOSOMAL HYDROLASES IN SHOCK

1979 ◽  
Vol 29 (1) ◽  
pp. 33-38
Author(s):  
RYO OGAWA ◽  
TAKASUKE IMAI ◽  
TATSUSHI FUJITA
Keyword(s):  
Lysosomal Enzymes ◽  
Lysosomal Hydrolases
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