Bardet–Biedl syndrome proteins 1 and 3 regulate the ciliary trafficking of polycystic kidney disease 1 protein
| Autor: | Maoqing Wu, Jing Zhou, Xuefeng Su, Anas Raed, Philip L. Beales, Gang Yao, Kaitlin Driscoll |
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| Rok vydání: | 2014 |
| Předmět: |
endocrine system
congenital hereditary and neonatal diseases and abnormalities medicine.medical_specialty TRPP Cation Channels BBSome BBS1 BBS5 Autosomal dominant polycystic kidney disease Biology Kidney Cell Line Gene Knockout Techniques Mice Bardet–Biedl syndrome Internal medicine Genetics medicine Polycystic kidney disease Animals Humans Cilia Molecular Biology Genetics (clinical) ADP-Ribosylation Factors Cilium Articles General Medicine medicine.disease Cell biology Protein Transport HEK293 Cells Endocrinology Membrane protein Microtubule-Associated Proteins |
| Zdroj: | Human Molecular Genetics. 23:5441-5451 |
| ISSN: | 1460-2083 0964-6906 |
| DOI: | 10.1093/hmg/ddu267 |
| Popis: | Bardet-Biedl syndrome (BBS) and autosomal dominant polycystic kidney disease (ADPKD) are two genetically distinct ciliopathies but share common phenotypes such as renal cysts. Seven BBS proteins form a complex called the BBSome which is localized at the basal body or ciliary axoneme and regulates the ciliary entry or flagellar exit of several signaling molecules. Here, we demonstrate that, unlike the seven-span somatostatin receptor 3 or the leptin receptor that interacts with all subunits of the BBSome, the ADPKD protein polycystin-1 (PC1) interacts with BBS1, BBS4, BBS5 and BBS8, four of the seven components of the BBSome. Only depletion or mutation of BBS1, but not depletion of BBS5 and BBS8, or knockout of BBS4, impairs ciliary trafficking of PC1 in kidney epithelial cells. Depletion of these BBS proteins affects neither the ciliary length nor the plasma membrane targeting of PC1. Expression of a pathogenic BBS3/Arl6 mutant (T31R) that locks Arl6 in the GDP form leads to stunted cilia and inhibition of PC1 on primary cilia. We propose that the 11-span membrane protein PC1 is a BBSome cargo and that the components of the BBSome may possess subunit-specific functions. Moreover, physical interactions between the BBS and ADPKD proteins may underline the overlapping renal phenotypes in these two diseases. |
| Databáze: | OpenAIRE |
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