RGD Reference Report - NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo during clathrin-mediated endocytosis. - Rat Genome Database

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NECAP 1 regulates AP-2 interactions to control vesicle size, number, and cargo during clathrin-mediated endocytosis.

Authors: Ritter, Brigitte  Murphy, Sebastian  Dokainish, Hatem  Girard, Martine  Gudheti, Manasa V  Kozlov, Guennadi  Halin, Marilene  Philie, Jacynthe  Jorgensen, Erik M  Gehring, Kalle  McPherson, Peter S 
Citation: Ritter B, etal., PLoS Biol. 2013 Oct;11(10):e1001670. doi: 10.1371/journal.pbio.1001670. Epub 2013 Oct 1.
RGD ID: 13432276
Pubmed: PMID:24130457   (View Abstract at PubMed)
PMCID: PMC3794858   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pbio.1001670   (Journal Full-text)

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 ß2-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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
presynaptic endocytosis involved_inIDA 13432276PMID:24130457SynGO 
presynaptic endocytosis involved_inIMP 13432276PMID:24130457SynGO 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:Q9CR9513432276; 13432276PMID:24130457IntAct 

Objects Annotated

Genes (Rattus norvegicus)
Amph  (amphiphysin)
Bin1  (bridging integrator 1)
Necap1  (NECAP endocytosis associated 1)


Additional Information