Document Detail

RNA interference in J774 macrophages reveals a role for coronin 1 in mycobacterial trafficking but not in actin-dependent processes.
MedLine Citation:
PMID:  18162581     Owner:  NLM     Status:  MEDLINE    
Macrophages are crucial for innate immunity, apoptosis, and tissue remodeling, processes that rely on the capacity of macrophages to internalize and process cargo through phagocytosis. Coronin 1, a member of the WD repeat protein family of coronins specifically expressed in leukocytes, was originally identified as a molecule that is recruited to mycobacterial phagosomes and prevents the delivery of mycobacteria to lysosomes, allowing these to survive within phagosomes. However, a role for coronin 1 in mycobacterial pathogenesis has been disputed in favor for its role in mediating phagocytosis and cell motility. In this study, a role for coronin 1 in actin-mediated cellular processes was addressed using RNA interference in the murine macrophage cell line J774. It is shown that the absence of coronin 1 in J774 macrophages expressing small interfering RNA constructs specific for coronin 1 does not affect phagocytosis, macropinocytosis, cell locomotion, or regulation of NADPH oxidase activity. However, in coronin 1-negative J774 cells, internalized mycobacteria were rapidly transferred to lysosomes and killed. Therefore, these results show that in J774 cells coronin 1 has a specific role in modulating phagosome-lysosome transport upon mycobacterial infection and that it is dispensable for most F-actin-mediated cytoskeletal rearrangements.
Rajesh Jayachandran; John Gatfield; Jan Massner; Imke Albrecht; Bettina Zanolari; Jean Pieters
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2007-12-27
Journal Detail:
Title:  Molecular biology of the cell     Volume:  19     ISSN:  1939-4586     ISO Abbreviation:  Mol. Biol. Cell     Publication Date:  2008 Mar 
Date Detail:
Created Date:  2008-02-29     Completed Date:  2008-11-10     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  9201390     Medline TA:  Mol Biol Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1241-51     Citation Subset:  IM    
Biozentrum, University of Basel, 4056 Basel, Switzerland.
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MeSH Terms
Actins / metabolism*
Cell Line
Chemotaxis / drug effects
Clone Cells
Epidermal Growth Factor / pharmacology
Erythrocytes / cytology,  drug effects
Gene Expression Regulation / drug effects
Macrophage Activation / drug effects
Macrophages / cytology*,  drug effects,  enzymology,  microbiology*
Microbial Viability / drug effects
Microfilament Proteins / genetics,  metabolism*
Mycobacterium / cytology,  drug effects,  physiology*
NADPH Oxidase / metabolism
Phagocytosis / drug effects
Pinocytosis / drug effects
Protein Transport / drug effects
Pseudopodia / drug effects,  metabolism
RNA Interference* / drug effects
RNA, Small Interfering / metabolism
Reg. No./Substance:
0/Actins; 0/Microfilament Proteins; 0/RNA, Small Interfering; 145420-64-0/coronin proteins; 62229-50-9/Epidermal Growth Factor; EC Oxidase

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

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