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Updated: Sep 28, 2025

In vivo and in vitro Studies of Adaptor-clathrin Interaction
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In vivo and in vitro Studies of Adaptor-clathrin Interaction

Published on: January 26, 2011

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Structural basis of an endocytic checkpoint that primes the AP2 clathrin adaptor for cargo internalization

Edward A Partlow1, Kevin S Cannon2, Gunther Hollopeter3

  • 1Department of Molecular Medicine, Cornell University, Ithaca, NY, USA.

Nature Structural & Molecular Biology
|March 29, 2022
PubMed

Insights

Clathrin-mediated endocytosis (CME) captures cargo using pioneer proteins called muniscin. Muniscin-engaged AP2 adaptor reorganizes to bind cargo, ensuring efficient internalization.

Area of Science:

  • Cell biology
  • Molecular mechanisms of endocytosis

Background:

  • Clathrin-mediated endocytosis (CME) is the primary pathway for plasma membrane internalization.
  • The AP2 clathrin adaptor's role in capturing transmembrane cargo for CME is not fully understood.

Purpose of the Study:

  • To elucidate the mechanism by which transmembrane cargos are captured to catalyze CME.
  • To investigate the role of pioneer proteins in AP2 adaptor function during endocytosis.

Main Methods:

  • Cryogenic-electron microscopy (cryo-EM) was employed to visualize structural rearrangements.
  • Analysis of mouse AP2 adaptor protein interactions with muniscin and cargo motifs.

Main Results:

  • A novel AP2 adaptor reorganization mechanism was discovered, exposing binding pockets for membrane and cargo.
  • Muniscin proteins were identified as stimulators of AP2 reorganization, independent of vesicle incorporation.
  • Muniscin-primed AP2 is poised for conformational change upon binding tyrosine internalization motifs (YxxΦ).

Conclusions:

  • Adaptor priming by muniscin acts as a critical checkpoint for cargo internalization during CME.
  • This mechanism ensures the efficient and specific capture of transmembrane cargo for cellular uptake.

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