INPP5E regulates phosphoinositide-dependent cilia transition zone function

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INPP5E regulates phosphoinositide-dependent cilia transition zone function

Human ciliopathies, including Joubert syndrome (JBTS), arise from cilia dysfunction. The inositol polyphosphate 5-phosphatase INPP5E localizes to cilia and is mutated in JBTS. Murine Inpp5e ablation is embryonically lethal and recapitulates JBTS, including neural tube defects and polydactyly; however, the underlying defects in cilia signaling and the function of INPP5E at cilia are still emergi...

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Ciliary Phosphoinositide Regulates Ciliary Protein Trafficking in Drosophila.

Cilia are highly specialized antennae-like cellular organelles. Inositol polyphosphate 5-phosphatase E (INPP5E) converts PI(4,5)P2 into PI4P and is required for proper ciliary function. Although Inpp5e mutations are associated with ciliopathies in humans and mice, the precise molecular role INPP5E plays in cilia remains unclear. Here, we report that Drosophila INPP5E (dINPP5E) regulates ciliary...

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Nephrocystin specifically localizes to the transition zone of renal and respiratory cilia and photoreceptor connecting cilia.

Nephronophthisis (NPHP) is a hereditary cystic kidney disorder that causes renal failure in children and young adults and can be associated with various extrarenal disorders, including retinitis pigmentosa. Six NPHP genes, whose functions are disrupted by autosomal recessive mutations in patients with NPHP, have been identified. The majority of patients with NPHP carry homozygous deletions of N...

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Phosphoinositides Regulate Ciliary Protein Trafficking to Modulate Hedgehog Signaling.

Primary cilia interpret vertebrate Hedgehog (Hh) signals. Why cilia are essential for signaling is unclear. One possibility is that some forms of signaling require a distinct membrane lipid composition, found at cilia. We found that the ciliary membrane contains a particular phosphoinositide, PI(4)P, whereas a different phosphoinositide, PI(4,5)P2, is restricted to the membrane of the ciliary b...

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INPP5E Preserves Genomic Stability through Regulation of Mitosis

The partially understood phosphoinositide signaling cascade regulates multiple aspects of cellular metabolism. Previous studies revealed that INPP5E, the inositol polyphosphate-5-phosphatase that is mutated in the developmental disorders Joubert and MORM syndromes, is essential for the function of the primary cilium and maintenance of phosphoinositide balance in nondividing cells. Here, we repo...

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ژورنال

عنوان ژورنال: Journal of Cell Biology

سال: 2016

ISSN: 0021-9525,1540-8140

DOI: 10.1083/jcb.201511055