| The role of calcium in lipoprotein release by the low-density lipoprotein receptor. | |
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MedLine Citation:
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PMID: 19583244 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The LDL receptor (LDLR) mediates efficient endocytosis of VLDL, VLDL remnants, and LDL. As part of the uptake process, the LDLR releases lipoproteins in endosomes. Released lipoproteins are subsequently trafficked to lysosomes for degradation, while the LDLR recycles back to the cell surface for further rounds of uptake. Endosomes have at least two features that can promote lipoprotein release: an acidic pH and low concentrations of free calcium. The relative contributions of acidic pH and low free calcium to lipoprotein release are not known. Here, we generated fibroblasts that express either normal LDLR or an LDLR variant that is unable to employ the acid-dependent release mechanism to determine the relative contributions of acidic pH and low free calcium on lipoprotein release. We show that endosomal concentrations of free calcium can drive lipoprotein release at rates that are similar to those of acid-dependent release and that the calcium-dependent and acid-dependent mechanisms can cooperate during lipoprotein release. Assessment of lipoprotein uptake by these two cell lines showed that LDL uptake requires the acid-dependent mechanism, while uptake of the VLDL remnant, beta-VLDL, does not. We propose that endosomes use both the acid-dependent and calcium-dependent release mechanisms to drive lipoprotein release and that the acid-dependent process is only required for LDL release. |
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Authors:
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Zhenze Zhao; Peter Michaely |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Biochemistry Volume: 48 ISSN: 1520-4995 ISO Abbreviation: Biochemistry Publication Date: 2009 Aug |
Date Detail:
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Created Date: 2009-08-31 Completed Date: 2009-11-02 Revised Date: 2011-05-05 |
Medline Journal Info:
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Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: United States |
Other Details:
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Languages: eng Pagination: 7313-24 Citation Subset: IM |
Affiliation:
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Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9039, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Calcium / metabolism* Cells, Cultured Endocytosis / physiology Endosomes / metabolism Fibroblasts / cytology, metabolism Gene Deletion Humans Hydrogen-Ion Concentration Lipoproteins / metabolism* Mice Monensin / metabolism Receptors, LDL / genetics, metabolism* |
| Grant Support | |
ID/Acronym/Agency:
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HL085218/HL/NHLBI NIH HHS; R01 HL085218-02/HL/NHLBI NIH HHS; R01 HL085218-03/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Lipoproteins; 0/Receptors, LDL; 17090-79-8/Monensin; 7440-70-2/Calcium |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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