Journal article
Functional characterization of Prickle2 and BBS7 identify overlapping phenotypes yet distinct mechanisms
Developmental biology, Vol.392(2), pp.245-255
08/15/2014
DOI: 10.1016/j.ydbio.2014.05.020
PMCID: PMC4114335
PMID: 24938409
Abstract
Ciliopathies are genetic disorders that are caused by dysfunctional cilia and affect multiple organs. One type of ciliopathy, Bardet–Biedl syndrome, is a rare disorder characterized by obesity, retinitis pigmentosa, polydactyly, mental retardation and susceptibility to cardiovascular diseases. The Wnt/Planar cell polarity (PCP) has been associated with cilia function and ciliogenesis in directing the orientation of cilia and basal bodies. Yet the exact relationship between PCP and ciliopathy is not well understood. Here, we examine interactions between a core PCP component, Prickle2 (Pk2), and a central BBS gene, Bbs7, using gene knockdown in the zebrafish. pk2 and bbs7 knockdown both disrupt the formation of a ciliated organ, the Kupffer׳s vesicle (KV), but do not display a synergistic interaction. By measuring cell polarity in the neural tube, we find that bbs7 activity is not required for Pk asymmetric localization. Moreover, BBS protein complex formation is preserved in the Pk2-deficient (Pk2−/−) mouse. Previously we reported an intracellular melanosome transport delay as a cardinal feature of reduced bbs gene activity. We find that pk2 knockdown suppresses bbs7-related retrograde transport delay. Similarly, knockdown of ift22, an anterograde intraflagellar transport component, also suppresses the bbs7-related retrograde delay. Notably, we find that pk2 knockdown larvae show a delay in anterograde transport. These data suggest a novel role for Pk2 in directional intracellular transport and our analyses show that PCP and BBS function independently, yet result in overlapping phenotypes when knocked down in zebrafish.
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•bbs7 and pk2 Both affect zebrafish neural tube polarity.•Bbs7 is not required for asymmetric Pk localization.•BBSome assembly is unperturbed in Pk2 knockout mice.•pk2 Knockdown suppresses bbs7-related retrograde melanosome transport defect.•Pk2 Modulates anterograde intracellular transport.
Details
- Title: Subtitle
- Functional characterization of Prickle2 and BBS7 identify overlapping phenotypes yet distinct mechanisms
- Creators
- Xue Mei - Department of Biology, University of Iowa, Iowa City, IA 52242, USATrudi A Westfall - Department of Biology, University of Iowa, Iowa City, IA 52242, USAQihong Zhang - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAVal C Sheffield - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USAAlexander G Bassuk - Department of Pediatrics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USADiane C Slusarski - Department of Biology, University of Iowa, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Developmental biology, Vol.392(2), pp.245-255
- DOI
- 10.1016/j.ydbio.2014.05.020
- PMID
- 24938409
- PMCID
- PMC4114335
- NLM abbreviation
- Dev Biol
- ISSN
- 0012-1606
- eISSN
- 1095-564X
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 08/15/2014
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Biology; Neurology (Pediatrics); Ophthalmology and Visual Sciences
- Record Identifier
- 9983991996002771
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