Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae
The Niemann-Pick C1 (NPC1) protein regulates cholesterol transport from late endosomes-lysosomes to other intracellular compartments. In this article, cholesterol transport to caveolin-1 and caveolin-2 containing compartments, such as the trans-Golgi network (TGN) and plasma membrane caveolae, was e...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2002-04-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520314875 |
| _version_ | 1818740195891085312 |
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| author | William S. Garver Kumar Krishnan Jayme R. Gallagos Makoto Michikawa Gordon A. Francis Randall A. Heidenreich |
| author_facet | William S. Garver Kumar Krishnan Jayme R. Gallagos Makoto Michikawa Gordon A. Francis Randall A. Heidenreich |
| author_sort | William S. Garver |
| collection | DOAJ |
| description | The Niemann-Pick C1 (NPC1) protein regulates cholesterol transport from late endosomes-lysosomes to other intracellular compartments. In this article, cholesterol transport to caveolin-1 and caveolin-2 containing compartments, such as the trans-Golgi network (TGN) and plasma membrane caveolae, was examined in normal (NPC+/+), NPC heterozygous (NPC+/−), and NPC homozygous (NPCm/−) human fibroblasts. The expression and distribution of NPC1 in each cell type were similar, and characterized by a finely dispersed, granular staining pattern. The expression of caveolin-1 and caveolin-2 was increased in NPC+/− and NPC−/− fibroblasts, although the distribution in each cell type was similar and characterized by predominant staining of the TGN and plasma membrane. The TGN in NPC+/+ fibroblasts was relatively cholesterol-enriched, whereas the TGN in NPC+/− and NPC−/− fibroblasts was partially or completely cholesterol-deficient, respectively. Consistent with studies demonstrating the transport of cholesterol from the TGN to plasma membrane caveolae, the concentration of cholesterol in plasma membrane caveolae isolated from NPC+/− and NPC−/− fibroblasts was significantly decreased, even though the total concentration of plasma membrane cholesterol in each cell type was similar. These studies demonstrate that NPC1 regulates cholesterol transport to caveolin-1 and caveolin-2 containing compartments such as the TGN and plasma membrane caveolae.—Garver, W. S., K. Krishnan, J. R. Gallagos, M. Michikawa, G. A. Francis, and R. A. Heidenreich. Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae. J. Lipid Res. 2002. 43: 579–589. |
| first_indexed | 2024-12-18T01:36:53Z |
| format | Article |
| id | doaj.art-d067eccfb88347b0a3a60b6a543fa48c |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-18T01:36:53Z |
| publishDate | 2002-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-d067eccfb88347b0a3a60b6a543fa48c2022-12-21T21:25:26ZengElsevierJournal of Lipid Research0022-22752002-04-01434579589Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolaeWilliam S. Garver0Kumar Krishnan1Jayme R. Gallagos2Makoto Michikawa3Gordon A. Francis4Randall A. Heidenreich5To whom correspondence should be addressed.; Department of Pediatrics, Arizona Health Sciences Center, The University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724Department of Pediatrics, Arizona Health Sciences Center, The University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724Department of Pediatrics, Arizona Health Sciences Center, The University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724Department of Dementia Research, National Institute for Longevity Sciences, 36-3 Gengo, Morioka, Obu, Aichi 474-8522, JapanCIHR Group on Molecular and Cell Biology of Lipids and Department of Medicine, University of Alberta, Edmonton, Alberta, Canada, T6G 2S2Department of Pediatrics, Arizona Health Sciences Center, The University of Arizona, 1501 N. Campbell Avenue, Tucson, AZ 85724The Niemann-Pick C1 (NPC1) protein regulates cholesterol transport from late endosomes-lysosomes to other intracellular compartments. In this article, cholesterol transport to caveolin-1 and caveolin-2 containing compartments, such as the trans-Golgi network (TGN) and plasma membrane caveolae, was examined in normal (NPC+/+), NPC heterozygous (NPC+/−), and NPC homozygous (NPCm/−) human fibroblasts. The expression and distribution of NPC1 in each cell type were similar, and characterized by a finely dispersed, granular staining pattern. The expression of caveolin-1 and caveolin-2 was increased in NPC+/− and NPC−/− fibroblasts, although the distribution in each cell type was similar and characterized by predominant staining of the TGN and plasma membrane. The TGN in NPC+/+ fibroblasts was relatively cholesterol-enriched, whereas the TGN in NPC+/− and NPC−/− fibroblasts was partially or completely cholesterol-deficient, respectively. Consistent with studies demonstrating the transport of cholesterol from the TGN to plasma membrane caveolae, the concentration of cholesterol in plasma membrane caveolae isolated from NPC+/− and NPC−/− fibroblasts was significantly decreased, even though the total concentration of plasma membrane cholesterol in each cell type was similar. These studies demonstrate that NPC1 regulates cholesterol transport to caveolin-1 and caveolin-2 containing compartments such as the TGN and plasma membrane caveolae.—Garver, W. S., K. Krishnan, J. R. Gallagos, M. Michikawa, G. A. Francis, and R. A. Heidenreich. Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae. J. Lipid Res. 2002. 43: 579–589.http://www.sciencedirect.com/science/article/pii/S0022227520314875caveolin-1caveolin-2fibroblasts |
| spellingShingle | William S. Garver Kumar Krishnan Jayme R. Gallagos Makoto Michikawa Gordon A. Francis Randall A. Heidenreich Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae Journal of Lipid Research caveolin-1 caveolin-2 fibroblasts |
| title | Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae |
| title_full | Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae |
| title_fullStr | Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae |
| title_full_unstemmed | Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae |
| title_short | Niemann-Pick C1 protein regulates cholesterol transport to the trans-Golgi network and plasma membrane caveolae |
| title_sort | niemann pick c1 protein regulates cholesterol transport to the trans golgi network and plasma membrane caveolae |
| topic | caveolin-1 caveolin-2 fibroblasts |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520314875 |
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