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| Subject Categories: Membranes & Transport | Cell & Tissue Architecture |
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| The EMBO Journal
(2005) 24, 2254–2264, doi:10.1038/sj.emboj.7600716 Published online 16 June 2005 |
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| A Rab21/LIM-only/CH-LIM complex regulates phagocytosis via both activating and inhibitory mechanisms |
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| Taruna Khurana, Joseph A Brzostowski1 and Alan R Kimmel |
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Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD, USA To whom correspondence should be addressed Alan R Kimmel, Laboratory of Cellular and Developmental Biology, National Institutes of Health, NIDDK, MMDS, Building 6/B1-22, NIH, Bethesda, MD 20892-2715, USA. Tel.: +1 301 496 3016; Fax: +1 301 496 5239; E-mail: ark1@helix.nih.gov 1 Present address: Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, MD, USA Received 20 January 2005; Accepted 24 May 2005; Published online 16 June 2005. |
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| Abstract |
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| We have identified two LIM domain proteins, LimF and ChLim, from Dictyostelium that interact with each other and with the small, Rab5-related, Rab21 GTPase to collectively regulate phagocytosis. To investigate in vivo functions, we generated cell lines that lack or overexpress LimF and ChLim and strains that express activating or inhibiting variants of Rab21. Overexpression of LimF, loss of ChLim, or expression of constitutively active Rab21 increases the rate of phagocytosis above that of wild type. Conversely, loss of LimF, overexpression of ChLim, or expression of a dominant-negative Rab21 inhibits phagocytosis. Our studies using cells carrying multiple mutations in these genes further indicate that ChLim antagonizes the activating function of Rab21-GTP during phagocytosis; in turn, LimF is required for Rab21-GTP function. Finally, we demonstrate that ChLim and LimF localize to the phagocytic cup and phago-lysosomal vesicles. We suggest that LimF, ChLim, and activated Rab21-GTP participate as a novel signaling complex that regulates phagocytic activity. |
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| Keywords: Dictyostelium, GTPases, phagocytosis, Rab21, vesicle formation |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHA Rab21/LIM-only/CH-LIM complex regulates phagocytosis via both activating and inhibitory mechanisms The EMBO Journal Article (06 Jul 2005) Calreticulin and calnexin in the endoplasmic reticulum are important for phagocytosis The EMBO Journal Article (03 Dec 2001) Functions of LIM proteins in cell polarity and chemotactic motility The EMBO Journal Article (15 Oct 2002) Structural basis for Rab GTPase activation by VPS9 domain exchange factors Nature Structural & Molecular Biology Article (01 May 2007) The Dictyostelium Bcr/Abr-related protein DRG regulates both Rac- and Rab-dependent pathways The EMBO Journal Article (02 Apr 2001) |
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