PUBLICATION
An Essential Role for DYF-11/MIP-T3 in Assembling Functional Intraflagellar Transport Complexes
- Authors
- Li, C., Inglis, P.N., Leitch, C.C., Efimenko, E., Zaghloul, N.A., Mok, C.A., Davis, E.E., Bialas, N.J., Healey, M.P., Héon, E., Zhen, M., Swoboda, P., Katsanis, N., and Leroux, M.R.
- ID
- ZDB-PUB-080331-10
- Date
- 2008
- Source
- PLoS Genetics 4(3): e1000044 (Journal)
- Registered Authors
- Katsanis, Nicholas, Zaghloul, Norann A.
- Keywords
- Cilia, Motor proteins, Embryos, Caenorhabditis elegans, Neuronal dendrites, Phenotypes, Somites, Zebrafish
- MeSH Terms
-
- Neurons, Afferent/physiology
- Cilia/physiology
- Mutation
- Biological Transport, Active
- DNA Primers/genetics
- PubMed
- 18369462 Full text @ PLoS Genet.
Abstract
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 backgding Kinesin-II, as well as IFT subcomplex A and B proteins, fail to enter ciliary axonemes and/or mislocalize, resulting in compromised cilirounds 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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