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Loss of cation-independent mannose 6-phosphate receptor expression promotes the accumulation of lysobisphosphatidic acid in multilamellar bodies

Barbara J Reaves, Paula Row, Nicholas A Bright, J Paul Luzio, Howard W Davidson

Journal of Cell Science, Volume: 113, Pages: 4099 - 4108

Swansea University Author: Paula Row

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Abstract

SUMMARYA number of recent studies have highlighted the importance of lipid domains within endocytic organelles in the sorting and movement of integral membrane proteins. In particular, considerable attention has become focussed upon the role of the unusual phospholipid lysobisphosphatidic acid (LBPA...

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Published in: Journal of Cell Science
ISSN: 0021-9533 1477-9137
Published: 2000
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URI: https://cronfa.swan.ac.uk/Record/cronfa18373
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spelling 2019-06-24T15:18:59.7603422 v2 18373 2014-09-10 Loss of cation-independent mannose 6-phosphate receptor expression promotes the accumulation of lysobisphosphatidic acid in multilamellar bodies 99bb528b2f8fb62aabbdad101d53ba96 Paula Row Paula Row true false 2014-09-10 BMS SUMMARYA number of recent studies have highlighted the importance of lipid domains within endocytic organelles in the sorting and movement of integral membrane proteins. In particular, considerable attention has become focussed upon the role of the unusual phospholipid lysobisphosphatidic acid (LBPA). This lipid appears to be directly involved in the trafficking of cholesterol and glycosphingolipids, and accumulates in a number of lysosomal storage disorders. Antibody-mediated disruption of LBPA function also leads to mis-sorting of cation-independent mannose 6-phosphate receptors. We now report that the converse is also true, and that spontaneous loss of cation-independent mannose 6- phosphate receptors from a rat fibroblast cell line led to the formation of aberrant late endocytic structures enriched in LBPA. Accumulation of LBPA was directly dependent upon the loss of the receptors, and could be reversed by expression of bovine cation-independent mannose 6- phosphate receptors in the mutant cell line.Ultrastructural analysis indicated that the abnormalorganelles were electron-dense, had a multi-lamellar structure, accumulated endocytosed probes, and were distinct from dense-core lysosomes present within the same cells. The late endocytic structures present at steady state within any particular cell likely reflect the balance of membrane traffic through the endocytic pathway of that cell, and the rate of maturation of individual endocytic organelles. Moreover, there is considerable evidence which suggests that cargo receptors also play a direct mechanistic role in membrane trafficking events. Therefore, loss of such a protein may disturb the overall equilibrium of the pathway, and hence cause the accumulation of aberrant organelles. We propose that this mechanism underlies the phenotype of the mutant cell line, and that the formation of inclusion bodies in many lysosomal storage diseases is also due to an imbalance in membrane trafficking within the endocytic pathway. Journal Article Journal of Cell Science 113 4099 4108 0021-9533 1477-9137 Mannose 6-phosphate receptor, Endosome, Lysosome, LBPA 31 12 2000 2000-12-31 http://jcs.biologists.org/content/113/22/4099.full.pdf COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University 2019-06-24T15:18:59.7603422 2014-09-10T13:02:53.3029995 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Barbara J Reaves 1 Paula Row 2 Nicholas A Bright 3 J Paul Luzio 4 Howard W Davidson 5
title Loss of cation-independent mannose 6-phosphate receptor expression promotes the accumulation of lysobisphosphatidic acid in multilamellar bodies
spellingShingle Loss of cation-independent mannose 6-phosphate receptor expression promotes the accumulation of lysobisphosphatidic acid in multilamellar bodies
Paula Row
title_short Loss of cation-independent mannose 6-phosphate receptor expression promotes the accumulation of lysobisphosphatidic acid in multilamellar bodies
title_full Loss of cation-independent mannose 6-phosphate receptor expression promotes the accumulation of lysobisphosphatidic acid in multilamellar bodies
title_fullStr Loss of cation-independent mannose 6-phosphate receptor expression promotes the accumulation of lysobisphosphatidic acid in multilamellar bodies
title_full_unstemmed Loss of cation-independent mannose 6-phosphate receptor expression promotes the accumulation of lysobisphosphatidic acid in multilamellar bodies
title_sort Loss of cation-independent mannose 6-phosphate receptor expression promotes the accumulation of lysobisphosphatidic acid in multilamellar bodies
author_id_str_mv 99bb528b2f8fb62aabbdad101d53ba96
author_id_fullname_str_mv 99bb528b2f8fb62aabbdad101d53ba96_***_Paula Row
author Paula Row
author2 Barbara J Reaves
Paula Row
Nicholas A Bright
J Paul Luzio
Howard W Davidson
format Journal article
container_title Journal of Cell Science
container_volume 113
container_start_page 4099
publishDate 2000
institution Swansea University
issn 0021-9533
1477-9137
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
url http://jcs.biologists.org/content/113/22/4099.full.pdf
document_store_str 0
active_str 0
description SUMMARYA number of recent studies have highlighted the importance of lipid domains within endocytic organelles in the sorting and movement of integral membrane proteins. In particular, considerable attention has become focussed upon the role of the unusual phospholipid lysobisphosphatidic acid (LBPA). This lipid appears to be directly involved in the trafficking of cholesterol and glycosphingolipids, and accumulates in a number of lysosomal storage disorders. Antibody-mediated disruption of LBPA function also leads to mis-sorting of cation-independent mannose 6-phosphate receptors. We now report that the converse is also true, and that spontaneous loss of cation-independent mannose 6- phosphate receptors from a rat fibroblast cell line led to the formation of aberrant late endocytic structures enriched in LBPA. Accumulation of LBPA was directly dependent upon the loss of the receptors, and could be reversed by expression of bovine cation-independent mannose 6- phosphate receptors in the mutant cell line.Ultrastructural analysis indicated that the abnormalorganelles were electron-dense, had a multi-lamellar structure, accumulated endocytosed probes, and were distinct from dense-core lysosomes present within the same cells. The late endocytic structures present at steady state within any particular cell likely reflect the balance of membrane traffic through the endocytic pathway of that cell, and the rate of maturation of individual endocytic organelles. Moreover, there is considerable evidence which suggests that cargo receptors also play a direct mechanistic role in membrane trafficking events. Therefore, loss of such a protein may disturb the overall equilibrium of the pathway, and hence cause the accumulation of aberrant organelles. We propose that this mechanism underlies the phenotype of the mutant cell line, and that the formation of inclusion bodies in many lysosomal storage diseases is also due to an imbalance in membrane trafficking within the endocytic pathway.
published_date 2000-12-31T03:21:32Z
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score 11.037144

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