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PMID:20448150

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Citation

Henne, WM, Boucrot, E, Meinecke, M, Evergren, E, Vallis, Y, Mittal, R and McMahon, HT (2010) FCHo proteins are nucleators of clathrin-mediated endocytosis. Science 328:1281-4

Abstract

Clathrin-mediated endocytosis, the major pathway for ligand internalization into eukaryotic cells, is thought to be initiated by the clustering of clathrin and adaptors around receptors destined for internalization. However, here we report that the membrane-sculpting F-BAR domain-containing Fer/Cip4 homology domain-only proteins 1 and 2 (FCHo1/2) were required for plasma membrane clathrin-coated vesicle (CCV) budding and marked sites of CCV formation. Changes in FCHo1/2 expression levels correlated directly with numbers of CCV budding events, ligand endocytosis, and synaptic vesicle marker recycling. FCHo1/2 proteins bound specifically to the plasma membrane and recruited the scaffold proteins eps15 and intersectin, which in turn engaged the adaptor complex AP2. The FCHo F-BAR membrane-bending activity was required, leading to the proposal that FCHo1/2 sculpt the initial bud site and recruit the clathrin machinery for CCV formation.

Links

PubMed PMC2883440 Online version:10.1126/science.1188462

Keywords

Adaptor Protein Complex 2/metabolism; Adaptor Proteins, Vesicular Transport/metabolism; Animals; Calcium-Binding Proteins/metabolism; Cell Line; Cell Membrane/metabolism; Cells, Cultured; Clathrin/metabolism; Clathrin-Coated Vesicles/metabolism; Endocytosis; HeLa Cells; Humans; Intracellular Signaling Peptides and Proteins/metabolism; Mice; Models, Molecular; Neurons/cytology; Neurons/metabolism; Phosphoproteins/metabolism; Protein Multimerization; Protein Structure, Tertiary; Proteins/chemistry; Proteins/metabolism; RNA Interference; Rats; Rats, Sprague-Dawley; Recombinant Fusion Proteins/metabolism; Synaptic Vesicles/metabolism

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:A7BFV9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q3UQN2

F

Seeded From UniProt

complete

RAT:FCHO2

located_in

GO:0098835: presynaptic endocytic zone membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

RAT:FCHO2

involved_in

GO:0048488: synaptic vesicle endocytosis

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:D3ZIM5
UniProtKB:Q3UQN2

P

  • occurs_in:(CL:0002608)

Seeded From UniProt

complete

HUMAN:FCHO1

is_active_in

GO:0005905: clathrin-coated pit

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:FCHO1

NOT|colocalizes_with

GO:0030136: clathrin-coated vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:FCHO1

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:FCHO1

involved_in

GO:0048268: clathrin coat assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FCHO1

involved_in

GO:0072583: clathrin-dependent endocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:EPS15

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q3UQN2

F

Seeded From UniProt

complete

HUMAN:FCHO2

involved_in

GO:0048268: clathrin coat assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:FCHO2

involved_in

GO:0072583: clathrin-dependent endocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:ITSN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q3UQN2

F

Seeded From UniProt

complete

MOUSE:FCHO2

is_active_in

GO:0005905: clathrin-coated pit

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FCHO2

involved_in

GO:0048488: synaptic vesicle endocytosis

ECO:0000316: genetic interaction evidence used in manual assertion

UniProtKB:D3ZIM5
UniProtKB:D3ZYR1

P

Seeded From UniProt

complete

MOUSE:FCHO2

enables

GO:0005546: phosphatidylinositol-4,5-bisphosphate binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

MOUSE:FCHO2

NOT|colocalizes_with

GO:0030136: clathrin-coated vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FCHO2

involved_in

GO:0010324: membrane invagination

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FCHO2

located_in

GO:0005886: plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

MOUSE:FCHO2

involved_in

GO:0072659: protein localization to plasma membrane

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

MOUSE:FCHO2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:A7BFV9

F

Seeded From UniProt

complete

MOUSE:FCHO2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P42566

F

Seeded From UniProt

complete

MOUSE:FCHO2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q15811

F

Seeded From UniProt

complete


See also

References

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