Document Detail


The role of calcium in lipoprotein release by the low-density lipoprotein receptor.
MedLine Citation:
PMID:  19583244     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Zhenze Zhao; Peter Michaely
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Biochemistry     Volume:  48     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-31     Completed Date:  2009-11-02     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  7313-24     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
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:
HL085218/HL/NHLBI NIH HHS; R01 HL085218/HL/NHLBI NIH HHS; R01 HL085218-02/HL/NHLBI NIH HHS; R01 HL085218-03/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Lipoproteins; 0/Receptors, LDL; 906O0YJ6ZP/Monensin; SY7Q814VUP/Calcium
Comments/Corrections

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