Browsing by Subject "Ciliopathy"

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    Cilia Signaling and Obesity
    (Elsevier, 2021) Engle, Staci E.; Bansal, Ruchi; Antonellis, Patrick J.; Berbari, Nicolas F.; Biology, School of Science
    An emerging number of rare genetic disorders termed ciliopathies are associated with pediatric obesity. It is becoming clear that the mechanisms associated with cilia dysfunction and obesity in these syndromes are complex. In addition to ciliopathic syndromic forms of obesity, several cilia-associated signaling gene mutations also lead to morbid obesity. While cilia have critical and diverse functions in energy homeostasis including their roles in centrally mediated food intake as well as in peripheral tissues, many questions remain. Here, we briefly discuss the syndromic ciliopathies and monoallelic cilia signaling gene mutations associated with obesity. We also describe potential ways cilia may be involved in common obesity. We discuss how neuronal cilia impact food intake potentially through leptin signaling and changes in ciliary G protein-coupled receptor (GPCR) signaling. We highlight several recent studies that have implicated the potential for cilia in peripheral tissues such as adipose and the pancreas to contribute to metabolic dysfunction. Then we discuss the potential for cilia to impact energy homeostasis through their roles in both development and adult tissue homeostasis. The studies discussed in this review highlight how a comprehensive understanding of the requirement of cilia for the regulation of diverse biological functions will contribute to our understanding of common forms of obesity.
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    Mks6 mutations reveal tissue- and cell type-specific roles for the cilia transition zone
    (Federation of American Society of Experimental Biology (FASEB), 2019-01) Lewis, Wesley R.; Bales, Katie L.; Revell, Dustin Z.; Croyle, Mandy J.; Engle, Staci E.; Song, Cheng Jack; Malarkey, Erik B.; Uytingco, Cedric R.; Shan, Dan; Antonellis, Patrick J.; Nagy, Tim R.; Kesterson, Robert A.; Mrug, Michal M.; Martens, Jeffrey R.; Berbari, Nicolas F.; Gross, Alecia K.; Yoder, Bradley K.; Biology, School of Science
    The transition zone (TZ) is a domain at the base of the cilium that is involved in maintaining ciliary compartment-specific sensory and signaling activity by regulating cilia protein composition. Mutations in TZ proteins result in cilia dysfunction, often causing pleiotropic effects observed in a group of human diseases classified as ciliopathies. The purpose of this study is to describe the importance of the TZ component Meckel-Grüber syndrome 6 (Mks6) in several organ systems and tissues regarding ciliogenesis and cilia maintenance using congenital and conditional mutant mouse models. Similar to MKS, congenital loss of Mks6 is embryonic lethal, displaying cilia loss and altered cytoskeletal microtubule modifications but only in specific cell types. Conditional Mks6 mutants have a variable cystic kidney phenotype along with severe retinal degeneration with mislocalization of phototransduction cascade proteins. However, other phenotypes, such as anosmia and obesity, which are typically associated with cilia and TZ dysfunction, were not evident. These data indicate that despite Mks6 being a core TZ component, it has tissue- or cell type-specific functions important for cilia formation and cilia sensory and signaling activities.