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An essential role for DYF-11/MIP-T3 in assembling functional intraflagellar transport complexes
Södertörns högskola, Institutionen för livsvetenskaper.
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2008 (engelsk)Inngår i: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 4, nr 3, s. e1000044-Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

MIP-T3 is a human protein found previously to associate with microtubules and the kinesin-interacting neuronal protein DISC1 ( Disrupted-in-Schizophrenia 1), but whose cellular function(s) remains unknown. Here we demonstrate that the C. elegans MIP-T3 ortholog DYF-11 is an intraflagellar transport (IFT) protein that plays a critical role in assembling functional kinesin motor-IFT particle complexes. We have cloned a loss of function dyf-11 mutant in which several key components of the IFT machinery, including Kinesin-II, as well as IFT subcomplex A and B proteins, fail to enter ciliary axonemes and/or mislocalize, resulting in compromised ciliary structures and sensory functions, and abnormal lipid accumulation. Analyses in different mutant backgrounds further suggest that DYF-11 functions as a novel component of IFT subcomplex B. Consistent with an evolutionarily conserved cilia-associated role, mammalian MIP-T3 localizes to basal bodies and cilia, and zebrafish mipt3 functions synergistically with the Bardet-Biedl syndrome protein Bbs4 to ensure proper gastrulation, a key cilium- and basal body-dependent developmental process. Our findings therefore implicate MIP-T3 in a previously unknown but critical role in cilium biogenesis and further highlight the emerging role of this organelle in vertebrate development.

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2008. Vol. 4, nr 3, s. e1000044-
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URN: urn:nbn:se:sh:diva-14165DOI: 10.1371/journal.pgen.1000044ISI: 000255407300004Scopus ID: 2-s2.0-41949085600OAI: oai:DiVA.org:sh-14165DiVA, id: diva2:466985
Tilgjengelig fra: 2011-12-18 Laget: 2011-12-16 Sist oppdatert: 2022-09-13bibliografisk kontrollert

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Efimenko, EvgeniSwoboda, Peter

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