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FASEB J. 2019 Jan;33(1):1440-1455. doi: 10.1096/fj.201801149R. Epub 2018 Aug 22.

Mks6 mutations reveal tissue- and cell type-specific roles for the cilia transition zone.

Author information

1
Department of Cell, Developmental, and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
2
Department of Optometry and Vision Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA.
3
Department of Biology, Indiana University-Purdue University Indianapolis, Indianapolis, Indiana, USA.
4
Department of Pharmacology and Therapeutics, College of Medicine, University of Florida, Gainesville, Florida, USA.
5
Division of Nephrology, Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, USA.
6
Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA; and.
7
Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Abstract

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-GrĂ¼ber 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. Lewis, W. R., Bales, K. L., Revell, D. Z., Croyle, M. J., Engle, S. E., Song, C. J., Malarkey, E. B., Uytingco, C. R., Shan, D., Antonellis, P. J., Nagy, T. R., Kesterson, R. A., Mrug, M. M., Martens, J. R., Berbari, N. F., Gross, A. K., Yoder, B. K. Mks6 mutations reveal tissue- and cell type-specific roles for the cilia transition zone.

KEYWORDS:

ciliopathy; cystic kidney disease; obesity; retinal degeneration

PMID:
30133325
PMCID:
PMC6355093
[Available on 2020-01-01]
DOI:
10.1096/fj.201801149R
[Indexed for MEDLINE]

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