TY - JOUR
T1 - Elipsa is an early determinant of ciliogenesis that links the IFT particle to membrane-associated small GTPase Rab8
AU - Omori, Yoshihiro
AU - Zhao, Chengtian
AU - Saras, Arunesh
AU - Mukhopadhyay, Saikat
AU - Kim, Woong
AU - Furukawa, Takahisa
AU - Sengupta, Piali
AU - Veraksa, Alexey
AU - Malicki, Jarema
N1 - Funding Information:
Tomer Avidor-Reiss, Lila Solnica-Krezel, Francesca Pignoni and Anneke Den Hollander provided helpful comments on an earlier version of this manuscript. We also thank Zac Pujic for help with mapping the elipsa locus; the Pignoni lab and Andria Schibler for excellent technical assistance; Joel Rosenbaum, Michael Rosbash and Emi Nagoshi for help with the imaging of nematode cilia; Iain Drummond for the anti-PC2 antibody; Marino Zerial and Juan Bonifacino for rabaptin clones; David Papermaster and James Goldenring for rab8 clones. These studies were supported by the National Eye Institute RO1 EY11882 and RO1 EY016859 awards (to J. M.) the National Institute on Deafness and other Communication Disorders RO1 DC005103 award (to J. M.), P30 NS44232 core grant to Brandeis University, National Institute of General Medical Sciences RO1 56223 (to P. S.), as well as a Knights Templar Pediatric Ophthalmology research grant (to Y. O.) and a core grant for Vision Research P30EY14104 to the Harvard Department of Ophthalmology.
PY - 2008
Y1 - 2008
N2 - The formation and function of cilia involves the movement of intraflagellar transport (IFT) particles underneath the ciliary membrane, along axonemal microtubules. Although this process has been studied extensively, its molecular basis remains incompletely understood. For example, it is unknown how the IFT particle interacts with transmembrane proteins. To study the IFT particle further, we examined elipsa, a locus characterized by mutations that cause particularly early ciliogenesis defects in zebrafish. We show here that elipsa encodes a coiled-coil polypeptide that localizes to cilia. Elipsa protein binds to Ift20, a component of IFT particles, and Elipsa homologue in Caenorhabditis elegans, DYF-11, translocates in sensory cilia, similarly to the IFT particle. This indicates that Elipsa is an IFT particle polypeptide. In the context of zebrafish embryogenesis, Elipsa interacts genetically with Rabaptin5, a well-studied regulator of endocytosis, which in turn interacts with Rab8, a small GTPase, known to localize to cilia. We show that Rabaptin5 binds to both Elipsa and Rab8, suggesting that these proteins provide a bridging mechanism between the IFT particle and protein complexes that assemble at the ciliary membrane.
AB - The formation and function of cilia involves the movement of intraflagellar transport (IFT) particles underneath the ciliary membrane, along axonemal microtubules. Although this process has been studied extensively, its molecular basis remains incompletely understood. For example, it is unknown how the IFT particle interacts with transmembrane proteins. To study the IFT particle further, we examined elipsa, a locus characterized by mutations that cause particularly early ciliogenesis defects in zebrafish. We show here that elipsa encodes a coiled-coil polypeptide that localizes to cilia. Elipsa protein binds to Ift20, a component of IFT particles, and Elipsa homologue in Caenorhabditis elegans, DYF-11, translocates in sensory cilia, similarly to the IFT particle. This indicates that Elipsa is an IFT particle polypeptide. In the context of zebrafish embryogenesis, Elipsa interacts genetically with Rabaptin5, a well-studied regulator of endocytosis, which in turn interacts with Rab8, a small GTPase, known to localize to cilia. We show that Rabaptin5 binds to both Elipsa and Rab8, suggesting that these proteins provide a bridging mechanism between the IFT particle and protein complexes that assemble at the ciliary membrane.
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U2 - 10.1038/ncb1706
DO - 10.1038/ncb1706
M3 - Article
C2 - 18364699
AN - SCOPUS:43149102968
SN - 1465-7392
VL - 10
SP - 437
EP - 444
JO - Nature cell biology
JF - Nature cell biology
IS - 4
ER -