Myristoylated CIL-7 is required for polycystin associated behaviors and extracellular vesicle biogenesis in C. elegans
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Maguire, Julie Elizabeth.
Myristoylated CIL-7 is required for polycystin associated behaviors and extracellular vesicle biogenesis in C. elegans. Retrieved from
https://doi.org/doi:10.7282/T3CR5W7WExport
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TitleMyristoylated CIL-7 is required for polycystin associated behaviors and extracellular vesicle biogenesis in C. elegans
Date Created2015
Other Date2015-05 (degree)
Extent1 online resource (vii, 74 p. : ill.)
DescriptionPKD-2 and LOV-1 are a putative mechanosensory transient receptor potential (TRP) channel-receptor polycystin complex that is required for C. elegans male mating behaviors. PKD-2 and LOV-1 localize to cilia found at the end of dendrites of male-specific sensory neurons, which include the CEMs in the head and the RnB neurons and the HOB neuron in the tail. pkd-2 and lov-1 mutants are defective in responding to hermaphrodites and locating the hermaphrodite vulva (Barr, DeModena et al. 2001). Mutations in PKD1 and PKD2, the human homologs of lov-1 and pkd-2, cause autosomal dominant polycystic kidney disease (ADPKD). As in C. elegans, the mammalian TRP polycystins localize to cilia on renal epithelial cells. The proper placement of PKD-2 to cilia involves several known factors, including LOV-1, intraflagellar transport, and the kinesin-3 KLP-6 (Bae, Qin et al. 2006, Peden, Barr 2005, Hu, Wittekind et al. 2007, Morsci, Barr 2011). The focus of my research revolved around two mutants, cil-7(my16) and cil-1(my15) that were identified through a forward genetic screen for PKD-2::GFP ciliary localization [Cil] defective mutants (Bae, Lyman-Gingerich et al. 2008, Bae, Qin et al. 2006). The emphasis of my research work was on the cil-7(my16) mutant. Loss of CIL-7 function resulted in a defect in the release of PKD-2::GFP containing extracellular vesicles (EVs) into the external environment, and transmission electron microscopy (TEM) showed that EVs remain trapped in the cephalic lumen. I showed that the myristoylation modification of CIL-7 is required for CIL-7 protein function in PKD-2 localization and C. elegans male mating behavior. CIL-7 myristoylation increases CIL-7 association as EV cargo. These studies firmly establish C. elegans as an ideal model in which to investigate EV cargo, such as CIL-7, and the acylation modifications that are necessary to become EV-associated.
NotePh.D.
NoteIncludes bibliographical references
Noteby Julie Elizabeth Maguire
Genretheses, ETD doctoral
Languageeng
CollectionGraduate School - New Brunswick Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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