An Essential Role for DYF-11/MIP-T3 in Assembling Functional Intraflagellar Transport Complexes

Resource type
Date created
2008-03
Authors/Contributors
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 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.
Document
Published as
Li C, Inglis PN, Leitch CC, Efimenko E, Zaghloul NA, et al. (2008) An Essential Role for DYF-11/MIP-T3 in Assembling Functional Intraflagellar Transport Complexes. PLoS Genet 4(3): e1000044. doi:10.1371/journal.pgen.1000044
Publication title
PLoS Genet
Document title
An Essential Role for DYF-11/MIP-T3 in Assembling Functional Intraflagellar Transport Complexes
Date
2008
Volume
4
Issue
3
Publisher DOI
10.1371/journal.pgen.1000044
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Copyright is held by the author(s).
Scholarly level
Peer reviewed?
Yes
Language
Member of collection
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Li-2008.pdf 680.9 KB