Sorting through the extensive and confusing roles of sortilin in metabolic disease
Sortilin is a post-Golgi trafficking receptor homologous to the yeast vacuolar protein sorting receptor 10 (VPS10). The VPS10 motif on sortilin is a 10-bladed β-propeller structure capable of binding more than 50 proteins, covering a wide range of biological functions including lipid and lipoprotein...
| Main Authors: | , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-08-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227522000761 |
| _version_ | 1828354933000241152 |
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| author | Kelly A. Mitok Mark P. Keller Alan D. Attie |
| author_facet | Kelly A. Mitok Mark P. Keller Alan D. Attie |
| author_sort | Kelly A. Mitok |
| collection | DOAJ |
| description | Sortilin is a post-Golgi trafficking receptor homologous to the yeast vacuolar protein sorting receptor 10 (VPS10). The VPS10 motif on sortilin is a 10-bladed β-propeller structure capable of binding more than 50 proteins, covering a wide range of biological functions including lipid and lipoprotein metabolism, neuronal growth and death, inflammation, and lysosomal degradation. Sortilin has a complex cellular trafficking itinerary, where it functions as a receptor in the trans-Golgi network, endosomes, secretory vesicles, multivesicular bodies, and at the cell surface. In addition, sortilin is associated with hypercholesterolemia, Alzheimer’s disease, prion diseases, Parkinson’s disease, and inflammation syndromes. The 1p13.3 locus containing SORT1, the gene encoding sortilin, carries the strongest association with LDL-C of all loci in human genome-wide association studies. However, the mechanism by which sortilin influences LDL-C is unclear. Here, we review the role sortilin plays in cardiovascular and metabolic diseases and describe in detail the large and often contradictory literature on the role of sortilin in the regulation of LDL-C levels. |
| first_indexed | 2024-04-14T02:32:55Z |
| format | Article |
| id | doaj.art-0f1f77c88d1d4de2b4607d797b5bfe0f |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-04-14T02:32:55Z |
| publishDate | 2022-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-0f1f77c88d1d4de2b4607d797b5bfe0f2022-12-22T02:17:36ZengElsevierJournal of Lipid Research0022-22752022-08-01638100243Sorting through the extensive and confusing roles of sortilin in metabolic diseaseKelly A. Mitok0Mark P. Keller1Alan D. Attie2Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USADepartment of Biochemistry, University of Wisconsin-Madison, Madison, WI, USAFor correspondence: Alan D. Attie; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI, USASortilin is a post-Golgi trafficking receptor homologous to the yeast vacuolar protein sorting receptor 10 (VPS10). The VPS10 motif on sortilin is a 10-bladed β-propeller structure capable of binding more than 50 proteins, covering a wide range of biological functions including lipid and lipoprotein metabolism, neuronal growth and death, inflammation, and lysosomal degradation. Sortilin has a complex cellular trafficking itinerary, where it functions as a receptor in the trans-Golgi network, endosomes, secretory vesicles, multivesicular bodies, and at the cell surface. In addition, sortilin is associated with hypercholesterolemia, Alzheimer’s disease, prion diseases, Parkinson’s disease, and inflammation syndromes. The 1p13.3 locus containing SORT1, the gene encoding sortilin, carries the strongest association with LDL-C of all loci in human genome-wide association studies. However, the mechanism by which sortilin influences LDL-C is unclear. Here, we review the role sortilin plays in cardiovascular and metabolic diseases and describe in detail the large and often contradictory literature on the role of sortilin in the regulation of LDL-C levels.http://www.sciencedirect.com/science/article/pii/S0022227522000761cholesterol/metabolismcholesterol/traffickingdyslipidemiasLDL/metabolismlipoproteins/metabolismsortilin |
| spellingShingle | Kelly A. Mitok Mark P. Keller Alan D. Attie Sorting through the extensive and confusing roles of sortilin in metabolic disease Journal of Lipid Research cholesterol/metabolism cholesterol/trafficking dyslipidemias LDL/metabolism lipoproteins/metabolism sortilin |
| title | Sorting through the extensive and confusing roles of sortilin in metabolic disease |
| title_full | Sorting through the extensive and confusing roles of sortilin in metabolic disease |
| title_fullStr | Sorting through the extensive and confusing roles of sortilin in metabolic disease |
| title_full_unstemmed | Sorting through the extensive and confusing roles of sortilin in metabolic disease |
| title_short | Sorting through the extensive and confusing roles of sortilin in metabolic disease |
| title_sort | sorting through the extensive and confusing roles of sortilin in metabolic disease |
| topic | cholesterol/metabolism cholesterol/trafficking dyslipidemias LDL/metabolism lipoproteins/metabolism sortilin |
| url | http://www.sciencedirect.com/science/article/pii/S0022227522000761 |
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