The N-Myc down regulated gene1 (NDRG1) is a Rab4a effector involved in vesicular recycling of E-cadherin

Sushant K. Kachhap, Dennis Faith, David Z. Qian, Shabana Shabbeer, Nathan L. Galloway, Roberto Pili, Samuel R. Denmeade, Angelo M. DeMarzo, Michael A. Carducci

Research output: Contribution to journalArticle

76 Citations (Scopus)

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 genel (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.

Original languageEnglish (US)
Article numbere844
JournalPLoS One
Volume2
Issue number9
DOIs
StatePublished - Sep 5 2007
Externally publishedYes

Fingerprint

cadherins
Recycling
Cadherins
recycling
Transferrin
transferrin
adhesion
Adhesion
cells
Down-Regulation
metastasis
Molecules
Tumor Suppressor Proteins
trans-Golgi Network
Endosomes
Mutant Proteins
mutants
Cell Adhesion
Confocal Microscopy
endosomes

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Kachhap, S. K., Faith, D., Qian, D. Z., Shabbeer, S., Galloway, N. L., Pili, R., ... Carducci, M. A. (2007). The N-Myc down regulated gene1 (NDRG1) is a Rab4a effector involved in vesicular recycling of E-cadherin. PLoS One, 2(9), [e844]. https://doi.org/10.1371/journal.pone.0000844

The N-Myc down regulated gene1 (NDRG1) is a Rab4a effector involved in vesicular recycling of E-cadherin. / Kachhap, Sushant K.; Faith, Dennis; Qian, David Z.; Shabbeer, Shabana; Galloway, Nathan L.; Pili, Roberto; Denmeade, Samuel R.; DeMarzo, Angelo M.; Carducci, Michael A.

In: PLoS One, Vol. 2, No. 9, e844, 05.09.2007.

Research output: Contribution to journalArticle

Kachhap, SK, Faith, D, Qian, DZ, Shabbeer, S, Galloway, NL, Pili, R, Denmeade, SR, DeMarzo, AM & Carducci, MA 2007, 'The N-Myc down regulated gene1 (NDRG1) is a Rab4a effector involved in vesicular recycling of E-cadherin', PLoS One, vol. 2, no. 9, e844. https://doi.org/10.1371/journal.pone.0000844
Kachhap, Sushant K. ; Faith, Dennis ; Qian, David Z. ; Shabbeer, Shabana ; Galloway, Nathan L. ; Pili, Roberto ; Denmeade, Samuel R. ; DeMarzo, Angelo M. ; Carducci, Michael A. / The N-Myc down regulated gene1 (NDRG1) is a Rab4a effector involved in vesicular recycling of E-cadherin. In: PLoS One. 2007 ; Vol. 2, No. 9.
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