| 著者 |
Barbelanne M, Lu Y, Kumar K, Zhang X, Li C, Park K, Warner A, Xu XZS, Shaham S, Leroux MR.
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| Abstract |
Primary (non-motile) cilia represent structurally and functionally diverse organelles whose roles as specialized cellular antenna are central to animal cell signaling pathways, sensory physiology and development. An ever-growing number of ciliary proteins, including those found in vertebrate photoreceptors, have been uncovered and linked to human disorders termed ciliopathies. Here, we demonstrate that an evolutionarily-conserved PPEF-family serine-threonine phosphatase, not functionally linked to cilia in any organism but associated with rhabdomeric (non-ciliary) photoreceptor degeneration in the Drosophila rdgC (retinal degeneration C) mutant, is a bona fide ciliary protein in C. elegans. The nematode protein, PEF-1, depends on transition zone proteins, which make up a 'ciliary gate' in the proximal-most region of the cilium, for its compartmentalization within cilia. Animals lacking PEF-1 protein function display structural defects to several types of cilia, including potential degeneration of microtubules. They also exhibit anomalies to cilium-dependent behaviors, including impaired responses to chemical, temperature, light, and noxious CO2 stimuli. Lastly, we demonstrate that PEF-1 function depends on conserved myristoylation and palmitoylation signals. Collectively, our findings broaden the role of PPEF proteins to include cilia, and suggest that the poorly-characterized mammalian PPEF1 and PPEF2 orthologs may also have ciliary functions and thus represent ciliopathy candidates.
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