NECAP 1 Regulates AP-2 Interactions to Control Vesicle Size, Number, and Cargo During Clathrin-Mediated Endocytosis Academic Article uri icon

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  • AP-2 is the core-organizing element in clathrin-mediated endocytosis. During the formation of clathrin-coated vesicles, clathrin and endocytic accessory proteins interact with AP-2 in a temporally and spatially controlled manner, yet it remains elusive as to how these interactions are regulated. Here, we demonstrate that the endocytic protein NECAP 1, which binds to the α-ear of AP-2 through a C-terminal WxxF motif, uses an N-terminal PH-like domain to compete with clathrin for access to the AP-2 β2-linker, revealing a means to allow AP-2-mediated coordination of accessory protein recruitment and clathrin polymerization at sites of vesicle formation. Knockdown and functional rescue studies demonstrate that through these interactions, NECAP 1 and AP-2 cooperate to increase the probability of clathrin-coated vesicle formation and to control the number, size, and cargo content of the vesicles. Together, our data demonstrate that NECAP 1 modulates the AP-2 interactome and reveal a new layer of organizational control within the endocytic machinery.


  • Ritter, Brigitte
  • Murphy, Sebastian
  • Dokainish, Hisham
  • Girard, Martine
  • Gudheti, Manasa V
  • Kozlov, Guennadi
  • Halin, Marilene
  • Philie, Jacynthe
  • Jorgensen, Erik M
  • Gehring, Kalle
  • McPherson, Peter S

publication date

  • October 2013

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