A synaptic molecular dependency network in knockdown of autism- and schizophrenia-associated genes revealed by multiplexed imaging.

ABSTRACT: The complex functions of neuronal synapses depend on their tightly interconnected protein network, and their dysregulation is implicated in the pathogenesis of autism spectrum disorders and schizophrenia. However, it remains unclear how synaptic molecular networks are altered biochemically in these disorders. Here, we apply multiplexed imaging to probe the effects of RNAi knockdown of 16 autism- and schizophrenia-associated genes on the simultaneous joint distribution of 10 synaptic proteins, observing several protein composition phenotypes associated with these risk genes. We apply Bayesian network analysis to infer hierarchical dependencies among eight excitatory synaptic proteins, yielding predictive relationships that can only be accessed with single-synapse, multiprotein measurements

SUBMITTER: Falkovich R 

PROVIDER: S-EPMC10259678 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature