Loss of Bardet-Biedl syndrome proteins causes synaptic aberrations in principal neurons.
Date
2019-09-01ICR Author
Author
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
Berbari NF
Type
Journal Article
Metadata
Show full item recordAbstract
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.
Collections
Subject
Animals
Anxiety
Bardet-Biedl Syndrome
Cytoskeletal Proteins
Dendritic Spines
Dentate Gyrus
Disease Models, Animal
Excitatory Postsynaptic Potentials
Female
Male
Memory
Mice
Receptor, IGF Type 1
Synaptosomes
Research team
Prote & Metabolomics Fac
Language
eng
Date accepted
2019-08-19
License start date
2019-09-01
Citation
PLoS Biology, 2019, 17 (9), pp. e3000414 -
Publisher
PUBLIC LIBRARY SCIENCE