PUBLICATION

Loss of the Bardet-Biedl protein Bbs1 alters photoreceptor outer segment protein and lipid composition

Authors
Masek, M., Etard, C., Hofmann, C., Hülsmeier, A.J., Zang, J., Takamiya, M., Gesemann, M., Neuhauss, S.C.F., Hornemann, T., Strähle, U., Bachmann-Gagescu, R.
ID
ZDB-PUB-220315-8
Date
2022
Source
Nature communications   13: 1282 (Journal)
Registered Authors
Bachmann-Gagescu, Ruxandra, Etard, Christelle, Masek, Markus, Neuhauss, Stephan, Strähle, Uwe, Takamiya, Masanari
Keywords
none
MeSH Terms
  • Cilia/metabolism
  • Animals
  • Microtubule-Associated Proteins/genetics
  • Microtubule-Associated Proteins/metabolism
  • Bardet-Biedl Syndrome*/genetics
  • Lipids
  • Zebrafish/metabolism
(all 7)
PubMed
35277505 Full text @ Nat. Commun.
Abstract
Primary cilia are key sensory organelles whose dysfunction leads to ciliopathy disorders such as Bardet-Biedl syndrome (BBS). Retinal degeneration is common in ciliopathies, since the outer segments (OSs) of photoreceptors are highly specialized primary cilia. BBS1, encoded by the most commonly mutated BBS-associated gene, is part of the BBSome protein complex. Using a bbs1 zebrafish mutant, we show that retinal development and photoreceptor differentiation are unaffected by Bbs1-loss, supported by an initially unaffected transcriptome. Quantitative proteomics and lipidomics on samples enriched for isolated OSs show that Bbs1 is required for BBSome-complex stability and that Bbs1-loss leads to accumulation of membrane-associated proteins in OSs, with enrichment in proteins involved in lipid homeostasis. Disruption of the tightly regulated OS lipid composition with increased OS cholesterol content are paralleled by early functional visual deficits, which precede progressive OS morphological anomalies. Our findings identify a role for Bbs1/BBSome in OS lipid homeostasis, suggesting a pathomechanism underlying retinal degeneration in BBS.
Genes / Markers
Figures
Figure Gallery (6 images)
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Expression
Phenotype
Mutations / Transgenics
Allele Construct Type Affected Genomic Region
ka742
    Small Deletion
    zf147TgTransgenic Insertion
      1 - 2 of 2
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      Human Disease / Model
      No data available
      Sequence Targeting Reagents
      Target Reagent Reagent Type
      bbs1CRISPR2-bbs1CRISPR
      1 - 1 of 1
      Show
      Fish
      Antibodies
      Orthology
      No data available
      Engineered Foreign Genes
      Marker Marker Type Name
      EGFPEFGEGFP
      1 - 1 of 1
      Show
      Mapping
      No data available