Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons.
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Embargo End Date
ICR Authors
Authors
Haq, N
Schmidt-Hieber, C
Sialana, FJ
Ciani, L
Heller, JP
Stewart, M
Bentley, L
Wells, S
Rodenburg, RJ
Nolan, PM
Forsythe, E
Wu, MC
Lubec, G
Salinas, P
Häusser, M
Beales, PL
Christou-Savina, S
Schmidt-Hieber, C
Sialana, FJ
Ciani, L
Heller, JP
Stewart, M
Bentley, L
Wells, S
Rodenburg, RJ
Nolan, PM
Forsythe, E
Wu, MC
Lubec, G
Salinas, P
Häusser, M
Beales, PL
Christou-Savina, S
Document Type
Journal Article
Date
2019-09-01
Date Accepted
2019-08-19
Abstract
Bardet-Biedl syndrome (BBS), a ciliopathy, is a rare genetic condition characterised by retinal degeneration, obesity, kidney failure, and cognitive impairment. In spite of progress made in our general understanding of BBS aetiology, the molecular and cellular mechanisms underlying cognitive impairment in BBS remain elusive. Here, we report that the loss of BBS proteins causes synaptic dysfunction in principal neurons, providing a possible explanation for the cognitive impairment phenotype observed in BBS patients. Using synaptosomal proteomics and immunocytochemistry, we demonstrate the presence of Bbs proteins in the postsynaptic density (PSD) of hippocampal neurons. Loss of Bbs results in a significant reduction of dendritic spines in principal neurons of Bbs mouse models. Furthermore, we show that spine deficiency correlates with events that destabilise spine architecture, such as impaired spine membrane receptor signalling, known to be involved in the maintenance of dendritic spines. Our findings suggest a role for BBS proteins in dendritic spine homeostasis that may be linked to the cognitive phenotype observed in BBS.
Citation
PLoS Biology, 2019, 17 (9), pp. e3000414 -
Source Title
PLoS Biology
Publisher
PUBLIC LIBRARY SCIENCE
ISSN
1544-9173
eISSN
1545-7885
1545-7885
1545-7885
Collections
Research Team
Prote & Metabolomics Fac