Work

The Role of Calcium in Lipoprotein Release by the Low-Density Lipoprotein Receptor

Year: 2009

Type: article

Abstract: 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.

Source: Biochemistry

DOI: 10.1021/bi900214u

Authors: Zhenze Zhao, Peter Michaely

Institution: The University of Texas Southwestern Medical Center

Language: English

Topic: Cholesterol and Lipid Metabolism

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funder: National Heart, Lung, and Blood Institute