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PMID:17786215

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Citation

Kachhap, SK, Faith, D, Qian, DZ, Shabbeer, S, Galloway, NL, Pili, R, Denmeade, SR, DeMarzo, AM and Carducci, MA (2007) The N-Myc down regulated Gene1 (NDRG1) Is a Rab4a effector involved in vesicular recycling of E-cadherin. PLoS ONE 2:e844

Abstract

Cell to cell adhesion is mediated by adhesion molecules present on the cell surface. Downregulation of molecules that form the adhesion complex is a characteristic of metastatic cancer cells. Downregulation of the N-myc down regulated gene1 (NDRG1) increases prostate and breast metastasis. The exact function of NDRG1 is not known. Here by using live cell confocal microscopy and in vitro reconstitution, we report that NDRG1 is involved in recycling the adhesion molecule E-cadherin thereby stabilizing it. Evidence is provided that NDRG1 recruits on recycling endosomes in the Trans Golgi network by binding to phosphotidylinositol 4-phosphate and interacts with membrane bound Rab4aGTPase. NDRG1 specifically interacts with constitutively active Rab4aQ67L mutant protein and not with GDP-bound Rab4aS22N mutant proving NDRG1 as a novel Rab4a effector. Transferrin recycling experiments reveals NDRG1 colocalizes with transferrin during the recycling phase. NDRG1 alters the kinetics of transferrin recycling in cells. NDRG1 knockdown cells show a delay in recycling transferrin, conversely NDRG1 overexpressing cells reveal an increase in rate of transferrin recycling. This novel finding of NDRG1 as a recycling protein involved with recycling of E-cadherin will aid in understanding NDRG1 role as a metastasis suppressor protein.

Links

PubMed PMC1952073 Online version:10.1371/journal.pone.0000844

Keywords

Cadherins/metabolism; Cell Cycle Proteins/genetics; Cell Cycle Proteins/physiology; Cell Line; Gene Knockdown Techniques; Humans; Immunohistochemistry; Intracellular Signaling Peptides and Proteins/genetics; Intracellular Signaling Peptides and Proteins/physiology; Microscopy, Confocal; Tissue Array Analysis; rab4 GTP-Binding Proteins/physiology

Significance

Annotations

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

HUMAN:APOA1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92597

F

Seeded From UniProt

complete

HUMAN:APOA2

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92597

F

Seeded From UniProt

complete

HUMAN:RTN1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92597

F

Seeded From UniProt

complete

HUMAN:NDRG1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q16799

F

Seeded From UniProt

complete

HUMAN:NDRG1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P02647

F

Seeded From UniProt

complete

HUMAN:NDRG1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q9UI14

F

Seeded From UniProt

complete

HUMAN:NDRG1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:P02652

F

Seeded From UniProt

complete

HUMAN:NDRG1

located_in

GO:0055038: recycling endosome membrane

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NDRG1

located_in

GO:0048471: perinuclear region of cytoplasm

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

HUMAN:NDRG1

enables

GO:0031267: small GTPase binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:NDRG1

enables

GO:0045296: cadherin binding

ECO:0000314: direct assay evidence used in manual assertion

F

Seeded From UniProt

complete

HUMAN:PRAF1

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q92597

F

Seeded From UniProt

complete


See also

References

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