Document Detail


Na+/H+ exchangers and RhoA regulate acidic extracellular pH-induced lysosome trafficking in prostate cancer cells.
MedLine Citation:
PMID:  19302267     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Acidic extracellular pH (pHe) is a common feature of the tumor microenvironment and has been implicated in tumor invasion through the induction of protease secretion.Since lysosomes constitute the major storehouse of cellular proteases, the trafficking of lysosomes to the cell periphery may be required in order to secrete proteases. We demonstrate that a pHe of 6.4-6.8 induced the trafficking of lysosomes to membrane protrusions in the cell periphery. This trafficking event depended upon the PI3K pathway, the GTPase RhoA and sodium-proton exchange activity, resulting in lysosomal exocytosis. Acidic pHe induced a cytoplasmic acidification (although cytoplasmic acidification was not sufficient for acidic pHe-induced lysosome trafficking and exocytosis) and inhibition of NHE activity with the amiloride derivative, EIPA or the anti-diabetic agent troglitazone prevented lysosome trafficking to the cell periphery. Interestingly, using the more specific NHE1 and NHE3 inhibitors, cariporide and s3226 respectively, we show that multiple NHE isoforms are involved in acidic pHe-induced lysosome trafficking and exocytosis. Moreover, in cells expressing NHE1 shRNA, although basal NHE activity was decreased, lysosomes still underwent acidic pHe-induced trafficking,suggesting compensation by other NHE family members.Together these data implicate proton exchangers, especially NHE1 and NHE3, in acidic pHe-induced lysosome trafficking and exocytosis.
Authors:
Joshua J Steffan; Jared L Snider; Omar Skalli; Tomas Welbourne; James A Cardelli
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Traffic (Copenhagen, Denmark)     Volume:  10     ISSN:  1600-0854     ISO Abbreviation:  Traffic     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-08-11     Completed Date:  2009-11-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100939340     Medline TA:  Traffic     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  737-53     Citation Subset:  IM    
Affiliation:
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport, LA 71130, USA.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Humans
Hydrogen-Ion Concentration
Lysosomes / metabolism*
Male
Prostatic Neoplasms / metabolism*,  pathology
Protein Transport
Sodium-Hydrogen Antiporter / physiology*
rhoA GTP-Binding Protein / physiology*
Grant Support
ID/Acronym/Agency:
R01 CA104242-01/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Sodium-Hydrogen Antiporter; EC 3.6.5.2/rhoA GTP-Binding Protein

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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