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

Published online

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Li, C; Inglis, PN; Leitch, CC; Efimenko, E; Zaghloul, NA; Mok, CA; Davis, EE; Bialas, NJ; Healey, MP; Héon, E; Zhen, M; Swoboda, P; Katsanis, N; Leroux, MR

Published Date

  • March 28, 2008

Published In

Volume / Issue

  • 4 / 3

Start / End Page

  • e1000044 -

PubMed ID

  • 18369462

Pubmed Central ID

  • 18369462

Electronic International Standard Serial Number (EISSN)

  • 1553-7404

Digital Object Identifier (DOI)

  • 10.1371/journal.pgen.1000044

Language

  • eng

Conference Location

  • United States