Article
- The EMBO Journal (2005) 24, 2254 - 2264
- doi:10.1038/sj.emboj.7600716
Published online: 16 June 2005
Subject Categories:
A Rab21/LIM-only/CH-LIM complex regulates phagocytosis via both activating and inhibitory mechanisms
Taruna Khurana1, Joseph A Brzostowski1,a and Alan R Kimmel1
- Laboratory of Cellular and Developmental Biology, NIDDK, National Institutes of Health, Bethesda, MD, USA
Correspondence to:
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
aPresent address: Laboratory of Immunogenetics, NIAID, National Institutes of Health, Rockville, MD, USA
Received 20 January 2005; Accepted 24 May 2005
Abstract
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.
Keywords:
- Dictyostelium,
- GTPases,
- phagocytosis,
- Rab21,
- vesicle formation
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