The N-Myc down regulated Gene1 (NDRG1) Is a Rab4a effector involved in vesicular recycling of E-cadherin
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...
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| Veröffentlicht in: | PloS one 2007-09, Vol.2 (9), p.e844-e844 |
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| creator | Kachhap, Sushant K Faith, Dennis Qian, David Z Shabbeer, Shabana Galloway, Nathan L Pili, Roberto Denmeade, Samuel R DeMarzo, Angelo M Carducci, Michael A |
| description | 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. |
| doi_str_mv | 10.1371/journal.pone.0000844 |
| format | Article |
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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.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0000844</identifier><identifier>PMID: 17786215</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Biosynthesis ; Cadherins - metabolism ; Cancer ; Cancer metastasis ; Cell adhesion ; Cell adhesion & migration ; Cell adhesion molecules ; Cell Biology/Cell Adhesion ; Cell Biology/Membranes and Sorting ; Cell Cycle Proteins - genetics ; Cell Cycle Proteins - physiology ; Cell Line ; Cell surface ; Colorectal cancer ; Confocal microscopy ; E-cadherin ; Endosomes ; Gene expression ; Gene Knockdown Techniques ; Golgi apparatus ; Humans ; Hypoxia ; Immunohistochemistry ; Intracellular Signaling Peptides and Proteins - genetics ; Intracellular Signaling Peptides and Proteins - physiology ; Kinetics ; Leukemia ; Liver cancer ; Medicine ; Metastases ; Metastasis ; Microscopy ; Microscopy, Confocal ; Myc protein ; Neurological Disorders/Neuromuscular Diseases ; Oncology/Prostate Cancer ; Pancreatic cancer ; Phosphatase ; Phosphates ; Prostate ; Prostate cancer ; Protein binding ; Protein turnover ; Proteins ; rab4 GTP-Binding Proteins - physiology ; Recycling ; Tissue Array Analysis ; Transferrin ; Transferrins ; Tumors</subject><ispartof>PloS one, 2007-09, Vol.2 (9), p.e844-e844</ispartof><rights>COPYRIGHT 2007 Public Library of Science</rights><rights>2007 Kachhap et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. 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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.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>17786215</pmid><doi>10.1371/journal.pone.0000844</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 1932-6203 |
| ispartof | PloS one, 2007-09, Vol.2 (9), p.e844-e844 |
| issn | 1932-6203 1932-6203 |
| language | eng |
| recordid | cdi_plos_journals_1950156049 |
| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Biosynthesis Cadherins - metabolism Cancer Cancer metastasis Cell adhesion Cell adhesion & migration Cell adhesion molecules Cell Biology/Cell Adhesion Cell Biology/Membranes and Sorting Cell Cycle Proteins - genetics Cell Cycle Proteins - physiology Cell Line Cell surface Colorectal cancer Confocal microscopy E-cadherin Endosomes Gene expression Gene Knockdown Techniques Golgi apparatus Humans Hypoxia Immunohistochemistry Intracellular Signaling Peptides and Proteins - genetics Intracellular Signaling Peptides and Proteins - physiology Kinetics Leukemia Liver cancer Medicine Metastases Metastasis Microscopy Microscopy, Confocal Myc protein Neurological Disorders/Neuromuscular Diseases Oncology/Prostate Cancer Pancreatic cancer Phosphatase Phosphates Prostate Prostate cancer Protein binding Protein turnover Proteins rab4 GTP-Binding Proteins - physiology Recycling Tissue Array Analysis Transferrin Transferrins Tumors |
| title | The N-Myc down regulated Gene1 (NDRG1) Is a Rab4a effector involved in vesicular recycling of E-cadherin |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-21T18%3A20%3A41IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=The%20N-Myc%20down%20regulated%20Gene1%20(NDRG1)%20Is%20a%20Rab4a%20effector%20involved%20in%20vesicular%20recycling%20of%20E-cadherin&rft.jtitle=PloS%20one&rft.au=Kachhap,%20Sushant%20K&rft.date=2007-09-05&rft.volume=2&rft.issue=9&rft.spage=e844&rft.epage=e844&rft.pages=e844-e844&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0000844&rft_dat=%3Cgale_plos_%3EA472247637%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1289163306&rft_id=info:pmid/17786215&rft_galeid=A472247637&rft_doaj_id=oai_doaj_org_article_dcd35240cb6441379a64b99eb4447834&rfr_iscdi=true |