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An evolutionarily conserved coiled-coil protein implicated in polycystic kidney disease is involved in basal body duplication and flagellar biogenesis in trypanosoma brucei.

Morgan, G. W. and Denny, P. W. and Vaughan, S. and Goulding, D. and Jeffries, T. R. and Smith, D. F. and Gull, K. and Field, M. C. (2005) 'An evolutionarily conserved coiled-coil protein implicated in polycystic kidney disease is involved in basal body duplication and flagellar biogenesis in trypanosoma brucei.', Molecular and cellular biology., 25 (9). pp. 3774-3783.

Abstract

Trypanosoma brucei is a flagellated protozoan with a highly polarized cellular structure. TbLRTP is a trypanosomal protein containing multiple SDS22-class leucine-rich repeats and a coiled-coil domain with high similarity to a mammalian testis-specific protein of unknown function. Homologues are present in a wide range of higher eukaryotes including zebra fish, where the gene product has been implicated in polycystic kidney disease. Western blot analysis and immunofluorescence with antibodies against recombinant TbLRTP indicate that the protein is expressed throughout the trypanosome life cycle and localizes to distal zones of the basal bodies. Overexpression and RNA interference demonstrate that TbLRTP is important for faithful basal body duplication and flagellum biogenesis. Expression of excess TbLRTP suppresses new flagellum assembly, while reduction of TbLRTP protein levels often results in the biogenesis of additional flagellar axonemes and paraflagellar rods that, most remarkably, are intracellular and fully contained within the cytoplasm. The mutant flagella are devoid of membrane and are often associated with four microtubules in an arrangement similar to that observed in the normal flagellar attachment zone. Aberrant basal body and flagellar biogenesis in TbLRTP mutants also influences cell size and cytokinesis. These findings demonstrate that TbLRTP suppresses basal body replication and subsequent flagellar biogenesis and indicate a critical role for the LRTP family of proteins in the control of the cell cycle. These data further underscore the role of aberrant flagellar biogenesis as a disease mechanism.

Item Type:Article
Keywords:Leucine-rich repeat, Cell-cycle, intraflagellar transport, African trypanosomes, RNA interference, Attachment zone, Segregation, Gene, cytokinesis, Mechanism.
Full text:Full text not available from this repository.
Publisher Web site:http://dx.doi.org/10.1128/MCB.25.9.3774-3783.2005
Record Created:11 May 2009 11:05
Last Modified:13 Jan 2014 16:24

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