An essential role for DYF-11/MIP-T3 in assembling functional intraflagellar transport complexes.

• Main Authors: Chunmei Li, Peter N Inglis, Carmen C Leitch, Evgeni Efimenko, Norann A Zaghloul, Calvin A Mok, Erica E Davis, Nathan J Bialas, Michael P Healey, Elise Héon, Mei Zhen, Peter Swoboda, Nicholas Katsanis, Michel R Leroux
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2008-03-01
• Series: PLoS Genetics
• Online Access: http://europepmc.org/articles/PMC2268012?pdf=render
• ISSN: 1553-7390; 1553-7404

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.