Unknown

Dataset Information

0

A tandem Di-hydrophobic motif mediates clathrin-dependent endocytosis via direct binding to the AP-2 ??2 subunits.


ABSTRACT: Select plasma membrane proteins can be marked as cargo for inclusion into clathrin-coated pits by common internalization signals (e.g. YXX?, dileucine motifs, NPXY) that serve as universal recognition sites for the AP-2 adaptor complex or other clathrin-associated sorting proteins. However, some surface proteins, such as the Kir2.3 potassium channel, lack canonical signals but are still targeted for clathrin-dependent endocytosis. Here, we explore the mechanism. We found an unusual endocytic signal in Kir2.3 that is based on two consecutive pairs of hydrophobic residues. Characterized by the sequence ??X?? (a tandem di-hydrophobic (TDH) motif, where ? is a hydrophobic amino acid), the signal shows no resemblance to other endocytic motifs, yet it directly interacts with AP-2 to target the Kir2.3 potassium channel into the endocytic pathway. We found that the tandem di-hydrophobic motif directly binds to the ??2 subunits of AP-2, interacting within a large hydrophobic cleft that encompasses part of the docking site for di-Leu signals, but includes additional structures. These observations expand the repertoire of clathrin-dependent internalization signals and the ways in which AP-2 can coordinate endocytosis of cargo proteins.

SUBMITTER: Ortega B 

PROVIDER: S-EPMC3411023 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

altmetric image

Publications

A tandem Di-hydrophobic motif mediates clathrin-dependent endocytosis via direct binding to the AP-2 ασ2 subunits.

Ortega Bernardo B   Mason Amanda K AK   Welling Paul A PA  

The Journal of biological chemistry 20120618 32


Select plasma membrane proteins can be marked as cargo for inclusion into clathrin-coated pits by common internalization signals (e.g. YXXΦ, dileucine motifs, NPXY) that serve as universal recognition sites for the AP-2 adaptor complex or other clathrin-associated sorting proteins. However, some surface proteins, such as the Kir2.3 potassium channel, lack canonical signals but are still targeted for clathrin-dependent endocytosis. Here, we explore the mechanism. We found an unusual endocytic sig  ...[more]

Similar Datasets

| S-EPMC2868873 | biostudies-literature
| S-EPMC3690600 | biostudies-literature
| S-EPMC2172816 | biostudies-other
| S-EPMC6773056 | biostudies-literature
| S-EPMC1360144 | biostudies-literature
| S-EPMC4269369 | biostudies-other
| S-EPMC3503507 | biostudies-literature
| S-EPMC8691179 | biostudies-literature
| S-EPMC5576906 | biostudies-literature
| S-EPMC150655 | biostudies-literature