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The Two Mannose 6-Phosphate Receptors Transport Distinct Complements of Lysosomal Proteins ()

Mammalian cells express two different mannose 6-phosphate receptors (MPR 46 and MPR 300), which both mediate targeting of Man-6-P-containing lysosomal proteins to lysosomes. To assess the contribution of either and both MPRs to the transport of lysosomal proteins, fibroblasts were established from m...

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Published in:	The Journal of biological chemistry 1995-11, Vol.270 (45), p.27311-27318
Main Authors:	Pohlmann, Regina, Boeker, Martin Wendland Christian, von Figura, Kurt
Format:	Article
Language:	English
Subjects:	Animals Biological Transport, Active Biomarkers Cathepsin D - metabolism Cells, Cultured Fibroblasts - metabolism Fibroblasts - ultrastructure Glucuronidase - metabolism Lysosomes - metabolism Mice Microscopy, Immunoelectron Protein Binding Proteins - metabolism Receptor, IGF Type 2 - deficiency Receptor, IGF Type 2 - genetics Receptor, IGF Type 2 - metabolism Solubility
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creator	Pohlmann, Regina Boeker, Martin Wendland Christian von Figura, Kurt
description	Mammalian cells express two different mannose 6-phosphate receptors (MPR 46 and MPR 300), which both mediate targeting of Man-6-P-containing lysosomal proteins to lysosomes. To assess the contribution of either and both MPRs to the transport of lysosomal proteins, fibroblasts were established from mouse embryos that were homozygous for disrupted alleles of either MPR 46 or MPR 300 or both MPRs. Fibroblasts missing both MPRs secreted most of the newly synthesized lysosomal proteins and were unable to maintain the catabolic function of lysosomes. The intracellular levels of lysosomal proteins decreased to
doi_str_mv	10.1074/jbc.270.45.27311
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To assess the contribution of either and both MPRs to the transport of lysosomal proteins, fibroblasts were established from mouse embryos that were homozygous for disrupted alleles of either MPR 46 or MPR 300 or both MPRs. Fibroblasts missing both MPRs secreted most of the newly synthesized lysosomal proteins and were unable to maintain the catabolic function of lysosomes. The intracellular levels of lysosomal proteins decreased to <20%, and undigested material accumulated in the lysosomal compartment. Fibroblasts lacking either MPR exhibited only a partial missorting and maintained, in general, half-normal to normal levels of lysosomal proteins. The same species of lysosomal proteins were found in secretions of double MPR-deficient fibroblasts as in secretions of single MPR-deficient fibroblasts, but at different ratios. This clearly indicates that neither MPR has an exclusive affinity for one or several lysosomal proteins. Furthermore, neither MPR can substitute in vivo for the loss of the other. It is proposed that the heterogeneity of the Man-6-P recognition marker within a lysosomal protein and among different lysosomal proteins has necessitated the evolution of two MPRs with complementary binding properties to ensure an efficient targeting of lysosomal proteins.</description><identifier>ISSN: 0021-9258</identifier><identifier>EISSN: 1083-351X</identifier><identifier>DOI: 10.1074/jbc.270.45.27311</identifier><identifier>PMID: 7592993</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Biological Transport, Active ; Biomarkers ; Cathepsin D - metabolism ; Cells, Cultured ; Fibroblasts - metabolism ; Fibroblasts - ultrastructure ; Glucuronidase - metabolism ; Lysosomes - metabolism ; Mice ; Microscopy, Immunoelectron ; Protein Binding ; Proteins - metabolism ; Receptor, IGF Type 2 - deficiency ; Receptor, IGF Type 2 - genetics ; Receptor, IGF Type 2 - metabolism ; Solubility</subject><ispartof>The Journal of biological chemistry, 1995-11, Vol.270 (45), p.27311-27318</ispartof><rights>1995 © 1995 ASBMB. 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To assess the contribution of either and both MPRs to the transport of lysosomal proteins, fibroblasts were established from mouse embryos that were homozygous for disrupted alleles of either MPR 46 or MPR 300 or both MPRs. Fibroblasts missing both MPRs secreted most of the newly synthesized lysosomal proteins and were unable to maintain the catabolic function of lysosomes. The intracellular levels of lysosomal proteins decreased to <20%, and undigested material accumulated in the lysosomal compartment. Fibroblasts lacking either MPR exhibited only a partial missorting and maintained, in general, half-normal to normal levels of lysosomal proteins. The same species of lysosomal proteins were found in secretions of double MPR-deficient fibroblasts as in secretions of single MPR-deficient fibroblasts, but at different ratios. This clearly indicates that neither MPR has an exclusive affinity for one or several lysosomal proteins. Furthermore, neither MPR can substitute in vivo for the loss of the other. It is proposed that the heterogeneity of the Man-6-P recognition marker within a lysosomal protein and among different lysosomal proteins has necessitated the evolution of two MPRs with complementary binding properties to ensure an efficient targeting of lysosomal proteins.</description><subject>Animals</subject><subject>Biological Transport, Active</subject><subject>Biomarkers</subject><subject>Cathepsin D - metabolism</subject><subject>Cells, Cultured</subject><subject>Fibroblasts - metabolism</subject><subject>Fibroblasts - ultrastructure</subject><subject>Glucuronidase - metabolism</subject><subject>Lysosomes - metabolism</subject><subject>Mice</subject><subject>Microscopy, Immunoelectron</subject><subject>Protein Binding</subject><subject>Proteins - metabolism</subject><subject>Receptor, IGF Type 2 - deficiency</subject><subject>Receptor, IGF Type 2 - genetics</subject><subject>Receptor, IGF Type 2 - metabolism</subject><subject>Solubility</subject><issn>0021-9258</issn><issn>1083-351X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1995</creationdate><recordtype>article</recordtype><recordid>eNqFkM-L1DAUx4Mo6-zq3YuQg4geOiZN0jTeZFxXYcRFRvAioU1fbZa2qXkZl_3vjTuDB2HZd_kevj94fAh5xtmaMy3fXLVuXWq2liqL4PwBWXFWi0Io_v0hWTFW8sKUqn5MThGvWD5p-Ak50cqUxogV-bEbgO6uA_3czHNAoFVxOQRchiYB_QoOlhQi0l1sZlxCTPS9x-Rnl-gmTMsIE8wJaejp9gYDhqkZ6WUMCfyM9NXrJ-RR34wIT496Rr59ON9tPhbbLxefNu-2hZNlzQtdyZoZx1RbOSOlcI71ojVtb7hotRYdM1WpStE3XBmQIKteKQWyLsE52XbijLw87C4x_NoDJjt5dDCOzQxhj1brymhVqnuDXDPOWKVzkB2CLgbECL1dop-aeGM5s3_R24zeZvRWKnuLPleeH7f37QTdv8KRdfZfHPzB_xyufQTb-uAGmP6feXuIQQb220O06DzMDrpcccl2wd_9wx9-Lp3I</recordid><startdate>19951110</startdate><enddate>19951110</enddate><creator>Pohlmann, Regina</creator><creator>Boeker, Martin Wendland Christian</creator><creator>von Figura, Kurt</creator><general>Elsevier Inc</general><general>American Society for Biochemistry and Molecular Biology</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>19951110</creationdate><title>The Two Mannose 6-Phosphate Receptors Transport Distinct Complements of Lysosomal Proteins ()</title><author>Pohlmann, Regina ; 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subjects	Animals Biological Transport, Active Biomarkers Cathepsin D - metabolism Cells, Cultured Fibroblasts - metabolism Fibroblasts - ultrastructure Glucuronidase - metabolism Lysosomes - metabolism Mice Microscopy, Immunoelectron Protein Binding Proteins - metabolism Receptor, IGF Type 2 - deficiency Receptor, IGF Type 2 - genetics Receptor, IGF Type 2 - metabolism Solubility
title	The Two Mannose 6-Phosphate Receptors Transport Distinct Complements of Lysosomal Proteins ()
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