Disabled-2 exhibits the properties of a cargo-selective endocytic clathrin adaptor

被引:246
作者
Mishra, SK [1 ]
Keyel, PA [1 ]
Hawryluk, MJ [1 ]
Agostinelli, NR [1 ]
Watkins, SC [1 ]
Traub, LM [1 ]
机构
[1] Univ Pittsburgh, Sch Med, Dept Cell Biol & Physiol, Pittsburgh, PA 15261 USA
关键词
cargo selection; clathrin; Disabled-2; phosphoinositide; receptor-mediated endocytosis;
D O I
10.1093/emboj/cdf487
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Clathrin-coated pits at the cell surface select material for transportation into the cell interior. A major mode of cargo selection at the bud site is via the mu2 subunit of the AP-2 adaptor complex, which recognizes tyrosine-based internalization signals. Other internalization motifs and signals, including phosphorylation and ubiquitylation, also tag certain proteins for incorporation into a coated vesicle, but the mechanism of selection is unclear. Disabled-2 (Dab2) recognizes the FXNPXY internalization motif in LDL-receptor family members via an N-terminal phosphotyrosine-binding (PTB) domain. Here, we show that in addition to binding AP-2, Dab2 also binds directly to phosphoinositides and to clathrin, assembling triskelia into regular polyhedral coats. The FXNPXY motif and phosphoinositides contact different regions of the PTB domain, but can stably anchor Dab2 to the membrane surface, while the distal AP-2 and clathrin-binding determinants regulate clathrin lattice assembly. We propose that Dab2 is a typical member of a growing family of cargo-specific adaptor proteins, including beta-arrestin, AP180, epsin, HIP1 and numb, which regulate clathrin-coat assembly at the plasma membrane by synchronizing cargo selection and lattice polymerization events.
引用
收藏
页码:4915 / 4926
页数:12
相关论文
共 66 条
[1]   CHARACTERIZATION OF ENDOCYTIC COMPARTMENTS USING THE HORSERADISH-PEROXIDASE DIAMINOBENZIDINE DENSITY SHIFT TECHNIQUE [J].
AJIOKA, RS ;
KAPLAN, J .
JOURNAL OF CELL BIOLOGY, 1987, 104 (01) :77-85
[2]   Coupled inositide phosphorylation and phospholipase D activation initiates clathrin-coat assembly on lysosomes [J].
Arneson, LS ;
Kunz, J ;
Anderson, RA ;
Traub, LM .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (25) :17794-17805
[3]   Molecular bases for the recognition of tyrosine-based sorting signals [J].
Bonifacino, JS ;
Dell'Angelica, EC .
JOURNAL OF CELL BIOLOGY, 1999, 145 (05) :923-926
[4]   Accessory protein recruitment motifs in clathrin-mediated endocytosis [J].
Brett, TJ ;
Traub, LM ;
Fremont, DH .
STRUCTURE, 2002, 10 (06) :797-809
[5]   Myosin VI isoform localized to clathrin-coated vesicles with a role in clathrin-mediated endocytosis [J].
Buss, F ;
Arden, SD ;
Lindsay, M ;
Luzio, JP ;
Kendrick-Jones, J .
EMBO JOURNAL, 2001, 20 (14) :3676-3684
[6]   Epsin is an EH-domain-binding protein implicated in clathrin-mediated endocytosis [J].
Chen, H ;
Fre, S ;
Slepnev, VI ;
Capua, MR ;
Takei, K ;
Butler, MH ;
Di Fiore, PP ;
De Camilli, P .
NATURE, 1998, 394 (6695) :793-797
[7]  
CHEN WJ, 1990, J BIOL CHEM, V265, P3116
[8]   Lipoprotein receptors: Signaling functions in the brain? [J].
Cooper, JA ;
Howell, BW .
CELL, 1999, 97 (06) :671-674
[9]   Assembly of clathrin coats disrupts the association between Eps15 and AP-2 adaptors [J].
Cupers, P ;
Jadhav, AP ;
Kirchhausen, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (04) :1847-1850
[10]   Molecular mechanism of NPF recognition by EH domains [J].
de Beer, T ;
Hoofnagle, AN ;
Enmon, JL ;
Bowers, RC ;
Yamabhai, M ;
Kay, BK ;
Overduin, M .
NATURE STRUCTURAL BIOLOGY, 2000, 7 (11) :1018-1022