The adaptor protein Dab2 sorts LDL receptors into coated pits independently of AP-2 and ARH

被引:141
作者
Maurer, Meghan E.
Cooper, Jonathan A.
机构
[1] Fred Hutchinson Canc Res Ctr, Div Basic Sci, Seattle, WA 98109 USA
[2] Fred Hutchinson Canc Res Ctr, Mol & Cellular Biol Program, Seattle, WA 98109 USA
关键词
AP-2; clathrin; CLASP; Dab2; ARH; LDL receptor adaptor protein; myosin VI;
D O I
10.1242/jcs.03217
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Clathrin-mediated endocytosis requires cargo-specific adaptor proteins that recognize specific receptors and recruit them into coated pits. ARH [also called low-density lipoprotein receptor (LDLR) adaptor protein] serves as an adaptor for LDLR endocytosis in liver. However, ARH is dispensable for LDL uptake by some other cell types. Here, we show that the adaptor Dab2 plays a major role in LDLR internalization in HeLa cells and fibroblasts. Dab2 mediates internalization of LDLRs but not transferrin receptors independently of ARH and the classic clathrin adaptor AP-2. If Dab2 is absent, ARH can mediate LDLR endocytosis, but its action requires AP-2. Furthermore, the rate of LDLR endocytosis is decreased when Dab2 is absent and Dab2, but not ARH, catalyzes the efficient clustering of LDLR into coated pits. Dab2 activity requires its binding to clathrin, LDLR and phospholipids. Dab2 is also involved in moving LDLRs off filopodia. We suggest that Dab2 is a cargo-specific endocytic adaptor protein, stably associating with phospholipids and clathrin to sort LDLR to nascentcoated pits, whereas ARH might accelerate later steps in LDLR endocytosis in cooperation with AP-2.
引用
收藏
页码:4235 / 4246
页数:12
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