Journal article
Photoreceptor cilia, in contrast to primary cilia, grant entry to a partially assembled BBSome
Human molecular genetics, Vol.30(1), pp.87-102
01/30/2021
DOI: 10.1093/hmg/ddaa284
PMID: 33517424
Abstract
Abstract The BBSome is a protein complex consisting of BBS1, BBS2, BBS4, BBS5, BBS7, BBS8, BBS9 and BBS18 that associates with intraflagellar transport complexes and specializes in ciliary trafficking. In primary cilia, ciliary entry requires the fully assembled BBSome as well as the small GTPase, ARL6 (BBS3). Retinal photoreceptors possess specialized cilia. In light of key structural and functional differences between primary and specialized cilia, we examined the principles of BBSome recruitment to photoreceptor cilia. We performed sucrose gradient fractionation using retinal lysates of Bbs2−/−, Bbs7−/−, Bbs8−/− and Bbs3−/− mice to determine the status of BBSome assembly, then determined localization of BBSome components using immunohistochemistry. Surprisingly, we found that a subcomplex of the BBSome containing at least BBS1, BBS5, BBS8 and BBS9 is recruited to cilia in the absence of BBS2 or BBS7. In contrast, a BBSome subcomplex consisting of BBS1, BBS2, BBS5, BBS7 and BBS9 is found in Bbs8−/− retinas and is denied ciliary entry in photoreceptor cells. In addition, the BBSome remains fully assembled in Bbs3−/− retinas and can be recruited to photoreceptor cilia in the absence of BBS3. We compared phenotypic severity of their retinal degeneration phenotypes. These findings demonstrate that unlike primary cilia, photoreceptor cilia admit a partially assembled BBSome meeting specific requirements. In addition, the recruitment of the BBSome to photoreceptor cilia does not require BBS3. These findings indicate that the ciliary entry of the BBSome is subjected to cell-specific regulation, particularly in cells with highly adapted forms of cilia such as photoreceptors.
Details
- Title: Subtitle
- Photoreceptor cilia, in contrast to primary cilia, grant entry to a partially assembled BBSome
- Creators
- Ying Hsu - Department of Pediatrics, Division of Medical Genetics and Genomics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USASeongjin Seo - Department of Ophthalmology and Visual Sciences, University of Iowa, Iowa City, IA 52242, USAVal C Sheffield - Department of Pediatrics, Division of Medical Genetics and Genomics, University of Iowa Carver College of Medicine, Iowa City, IA 52242, USA
- Resource Type
- Journal article
- Publication Details
- Human molecular genetics, Vol.30(1), pp.87-102
- DOI
- 10.1093/hmg/ddaa284
- PMID
- 33517424
- NLM abbreviation
- Hum Mol Genet
- ISSN
- 0964-6906
- eISSN
- 1460-2083
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: R01 EY011298, R01 EY017168, R01 EY022616, R21 EY027431, P30 EY025580; DOI: 10.13039/100001024, name: Roy J. Carver Charitable Trust
- Language
- English
- Date published
- 01/30/2021
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Ophthalmology and Visual Sciences
- Record Identifier
- 9984070311102771
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