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- Schafer, J C, et al.
(författare)
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XBX-1 encodes a dynein light intermediate chain required for retrograde intraflagellar transport and cilia assembly in Caenorhabditis elegans
- 2003
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Ingår i: Molecular Biology of the Cell. - 1059-1524 .- 1939-4586. ; 14:5, s. 2057-2070
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Tidskriftsartikel (refereegranskat)abstract
- Intraflagellar transport (IFT) is a process required for flagella and cilia assembly that describes the dynein and kinesin mediated movement of particles along axonemes that consists of an A and a B complex, defects in which disrupt retrograde and anterograde transport, respectively. Herein, we describe a novel Caenorhabditis elegans gene, xbx-1, that is required for retrograde IFT and shares homology with a mammalian dynein light intermediate chain (D2LIC). xbx-1 expression in ciliated sensory neurons is regulated by the transcription factor DAF-19, as demonstrated previously for genes encoding IFT complex B proteins. XBX-1 localizes to the base of the cilia and undergoes anterograde and retrograde movement along the axoneme. Disruption of xbx-1 results in cilia defects and causes behavioral abnormalities observed in other cilia mutants. Analysis of cilia in xbx-1 mutants reveals that they are shortened and have a bulb like structure in which IFT proteins accumulate. The role of XBX-1 in IFT was further confirmed by analyzing the effect that other IFT mutations have on XBX-1 localization and movement. In contrast to other IFT proteins, retrograde XBX-1 movement was detected in complex A mutants. Our results suggest that the DLIC protein XBX-1 functions together with the CHE-3 dynein in retrograde IFT, downstream of the complex A proteins.
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| 2. |
- Winkelbauer, M E, et al.
(författare)
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The C-elegans homologs of nephrocystin-1 and nephrocystin-4 are cilia transition zone proteins involved in chemosensory perception
- 2005
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Ingår i: Journal of Cell Science. - : The Company of Biologists. - 0021-9533 .- 1477-9137. ; 118:23, s. 5575-5587
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Tidskriftsartikel (refereegranskat)abstract
- Nephronophthisis (NPH) is a cystic kidney disorder that causes end-stage renal failure in children. Five nephrocystin (nephrocystin-1 to nephrocystin-5) genes, whose function is disrupted in NPH patients, have been identified and data indicate they form a complex at cell junctions and focal adhesions. More recently, the nephrocystin proteins have also been identified in cilia, as have multiple other cystic kidney disease related proteins. Significant insights into this cilia and cystic kidney disease connection have come from analyses in simpler eukaryotic organisms such as Caenorhabditis elegans. In this regard, we became interested in the C elegans homologs of nephrocystin-1 (nph-1) and nephrocystin-4 (nph-4) from a database screen to identify genes coordinately regulated by the ciliogenic transcription factor DAF-19. Here we show that expression of nph-1 and nph-4 is DAF-19 dependent, that their expression is restricted to ciliated sensory neurons, and that both NPH-1 and NPH-4 concentrate at the transition zones at the base of the cilia, but are not found in the cilium axoneme. In addition, NPH-4 is required for the localization of NPH-1 to this domain. Interestingly, nph-1 or nph-4 mutants have no obvious cilia assembly defects; however, they do have abnormalities in cilia-mediated sensory functions as evidenced by abnormal chemotaxis and lifespan regulation. Our data suggest that rather than having a ciliogenic role, the NPH proteins play an important function as part of the sensory or signaling machinery of this organelle. These findings suggest that the defects in human NPH patients may not be the result of aberrant ciliogenesis but abnormal cilia-sensory functions.
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