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Abstract
Plasticity in sensory signaling is partly mediated via regulated trafficking of signaling molecules to and from primary cilia. Tubby-related proteins regulate ciliary protein transport; however, their roles in remodeling cilia properties are not fully understood. We find that the C. elegans TUB-1 Tubby homolog regulates membrane morphogenesis and signaling protein transport in specialized sensory cilia. In particular, TUB-1 is essential for sensory signaling-dependent reshaping of olfactory cilia morphology. We show that compromised sensory signaling alters cilia membrane phosphoinositide composition via TUB-1-dependent trafficking of a PIP5 kinase. TUB-1 regulates localization of this lipid kinase at the cilia base in part via localization of the AP-2 adaptor complex subunit DPY-23. Our results describe new functions for Tubby proteins in the dynamic regulation of cilia membrane lipid composition, morphology, and signaling protein content, and suggest that this conserved family of proteins plays a critical role in mediating cilia structural and functional plasticity.
Highlights
Primary cilia are sensory organelles that are specialized to detect and transduce external stimuli (Bangs and Anderson, 2017; Hilgendorf et al, 2016; May-Simera et al, 2017)
Our results identify the conserved TUB-1 Tubby protein as a key regulator of membrane biogenesis in specialized cilia, demonstrate that cilia membrane phosphoinositide composition is subject to dynamic modulation as a function of sensory input, and describe a new function for TUB-1 in regulating cilia membrane lipid and protein content via regulated trafficking of a lipid kinase
AWA cilia complexity was reduced in tub-1 mutants; we observed branches emanating from the AWA periciliary membrane compartment (PCMC) in these animals (Figure 1A)
Summary
Primary cilia are sensory organelles that are specialized to detect and transduce external stimuli (Bangs and Anderson, 2017; Hilgendorf et al, 2016; May-Simera et al, 2017). Cilia membrane volume and signaling protein content is regulated dynamically both as a function of cell type and external stimuli (Doroquez et al, 2014; Falk et al, 2015; Goetz et al, 2009; Mesland et al, 1980; Mukhopadhyay et al, 2008; Mykytyn and Askwith, 2017; Silverman and Leroux, 2009). Sonic Hedgehog (Shh) signaling regulates ciliary trafficking of the Smoothened and GPR161 G-protein-coupled receptors (GPCRs), as well as the Shh receptor Patched (Bangs and Anderson, 2017; Corbit et al, 2005; Huangfu et al, 2003; Mukhopadhyay et al, 2013; Rohatgi et al, 2007).
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