Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export
LAMP1 and LAMP2 proteins are highly abundant, ubiquitous, mammalian proteins that line the lysosome limiting membrane, and protect it from lysosomal hydrolase action. LAMP2 deficiency causes Danon’s disease, an X-linked hypertrophic cardiomyopathy. LAMP2 is needed for chaperone-mediated autophagy, a...
| Main Authors: | , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2016-09-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/21635 |
| _version_ | 1811181070163378176 |
|---|---|
| author | Jian Li Suzanne R Pfeffer |
| author_facet | Jian Li Suzanne R Pfeffer |
| author_sort | Jian Li |
| collection | DOAJ |
| description | LAMP1 and LAMP2 proteins are highly abundant, ubiquitous, mammalian proteins that line the lysosome limiting membrane, and protect it from lysosomal hydrolase action. LAMP2 deficiency causes Danon’s disease, an X-linked hypertrophic cardiomyopathy. LAMP2 is needed for chaperone-mediated autophagy, and its expression improves tissue function in models of aging. We show here that human LAMP1 and LAMP2 bind cholesterol in a manner that buries the cholesterol 3β-hydroxyl group; they also bind tightly to NPC1 and NPC2 proteins that export cholesterol from lysosomes. Quantitation of cellular LAMP2 and NPC1 protein levels suggest that LAMP proteins represent a significant cholesterol binding site at the lysosome limiting membrane, and may signal cholesterol availability. Functional rescue experiments show that the ability of human LAMP2 to facilitate cholesterol export from lysosomes relies on its ability to bind cholesterol directly. |
| first_indexed | 2024-04-11T09:13:28Z |
| format | Article |
| id | doaj.art-12f07e014e47450a9450dd4fa7559adf |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:13:28Z |
| publishDate | 2016-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-12f07e014e47450a9450dd4fa7559adf2022-12-22T04:32:26ZengeLife Sciences Publications LtdeLife2050-084X2016-09-01510.7554/eLife.21635Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol exportJian Li0Suzanne R Pfeffer1https://orcid.org/0000-0002-6462-984XDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United StatesDepartment of Biochemistry, Stanford University School of Medicine, Stanford, United StatesLAMP1 and LAMP2 proteins are highly abundant, ubiquitous, mammalian proteins that line the lysosome limiting membrane, and protect it from lysosomal hydrolase action. LAMP2 deficiency causes Danon’s disease, an X-linked hypertrophic cardiomyopathy. LAMP2 is needed for chaperone-mediated autophagy, and its expression improves tissue function in models of aging. We show here that human LAMP1 and LAMP2 bind cholesterol in a manner that buries the cholesterol 3β-hydroxyl group; they also bind tightly to NPC1 and NPC2 proteins that export cholesterol from lysosomes. Quantitation of cellular LAMP2 and NPC1 protein levels suggest that LAMP proteins represent a significant cholesterol binding site at the lysosome limiting membrane, and may signal cholesterol availability. Functional rescue experiments show that the ability of human LAMP2 to facilitate cholesterol export from lysosomes relies on its ability to bind cholesterol directly.https://elifesciences.org/articles/21635cholesterollysosome membraneNiemann Pick diseaseglycocalyx |
| spellingShingle | Jian Li Suzanne R Pfeffer Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export eLife cholesterol lysosome membrane Niemann Pick disease glycocalyx |
| title | Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export |
| title_full | Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export |
| title_fullStr | Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export |
| title_full_unstemmed | Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export |
| title_short | Lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export |
| title_sort | lysosomal membrane glycoproteins bind cholesterol and contribute to lysosomal cholesterol export |
| topic | cholesterol lysosome membrane Niemann Pick disease glycocalyx |
| url | https://elifesciences.org/articles/21635 |
| work_keys_str_mv | AT jianli lysosomalmembraneglycoproteinsbindcholesterolandcontributetolysosomalcholesterolexport AT suzannerpfeffer lysosomalmembraneglycoproteinsbindcholesterolandcontributetolysosomalcholesterolexport |