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PMID:15703209

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Citation

Soulet, F, Yarar, D, Leonard, M and Schmid, SL (2005) SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis. Mol. Biol. Cell 16:2058-67

Abstract

Dynamin, a central player in clathrin-mediated endocytosis, interacts with several functionally diverse SH3 domain-containing proteins. However, the role of these interactions with regard to dynamin function is poorly defined. We have investigated a recently identified protein partner of dynamin, SNX9, sorting nexin 9. SNX9 binds directly to both dynamin-1 and dynamin-2. Moreover by stimulating dynamin assembly, SNX9 stimulates dynamin's basal GTPase activity and potentiates assembly-stimulated GTPase activity on liposomes. In fixed cells, we observe that SNX9 partially localizes to clathrin-coated pits. Using total internal reflection fluorescence microscopy in living cells, we detect a transient burst of EGFP-SNX9 recruitment to clathrin-coated pits that occurs during the late stages of vesicle formation and coincides spatially and temporally with a burst of dynamin-mRFP fluorescence. Transferrin internalization is inhibited in HeLa cells after siRNA-mediated knockdown of SNX9. Thus, our results establish that SNX9 is required for efficient clathrin-mediated endocytosis and suggest that it functions to regulate dynamin activity.

Links

PubMed PMC1073683 Online version:10.1091/mbc.E04-11-1016

Keywords

Carrier Proteins/genetics; Carrier Proteins/metabolism; Cell Membrane/metabolism; Clathrin/metabolism; Coated Pits, Cell-Membrane/metabolism; Dynamin I/chemistry; Dynamin I/genetics; Dynamin I/metabolism; Dynamin II/chemistry; Dynamin II/genetics; Dynamin II/metabolism; Endocytosis; GTP Phosphohydrolases/metabolism; HeLa Cells; Humans; Liposomes/metabolism; Protein Binding; Receptors, Transferrin/metabolism; Sorting Nexins; Vesicular Transport Proteins

Significance

Annotations

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

HUMAN:DYN2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9Y5X1

F

Seeded From UniProt

complete

HUMAN:SNX9

located_in

GO:0031234: extrinsic component of cytoplasmic side of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SNX9

located_in

GO:0031410: cytoplasmic vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SNX9

located_in

GO:0005802: trans-Golgi network

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SNX9

involved_in

GO:0065003: protein-containing complex assembly

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SNX9

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P50570

F

Seeded From UniProt

complete

HUMAN:SNX9

part_of

GO:0005802: trans-Golgi network

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SNX9

involved_in

GO:0006886: intracellular protein transport

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SNX9

involved_in

GO:0006898: receptor-mediated endocytosis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SNX9

part_of

GO:0031410: cytoplasmic vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SNX9

colocalizes_with

GO:0030136: clathrin-coated vesicle

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SNX9

part_of

GO:0031234: extrinsic component of cytoplasmic side of plasma membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:SNX9

involved_in

GO:0032461: positive regulation of protein oligomerization

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete

HUMAN:SNX9

involved_in

GO:0043547: positive regulation of GTPase activity

ECO:0000314: direct assay evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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