In situ Proteomics Unveils Specialized Domains for Extrasynaptic Signaling on Neuronal Cilia

ABSTRACT: Neuronal cilia have emerged as signaling hubs, but their molecular composition and integration with synaptic communication remain unexplored. Using an engineered Arl13b-TurboID mouse model, we achieved robust cilia-specific biotinylation and proteomic profiling across diverse cell types. Comparative analyses revealed that brain and kidney cilia share only half of their proteome, with neuronal cilia uniquely enriched in synaptic proteins, adhesion molecules, and neurotransmitter receptors. Surprisingly, several signaling and adhesion molecules localize to neuronal cilia in discrete patterns maintained by active retrieval mechanisms. 16-fold expansion microscopy of mouse cortex revealed that the NMDA receptor is non-randomly positioned on ciliary membranes near glutamatergic synapses, suggesting that cilia eavesdrop on synaptic activity. These findings highlight the diversity and specialization of mammalian ciliary proteomes and indicates that nanoscale organization may endow neuronal cilia with extrasynaptic functions.

INSTRUMENT(S):

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain, Neuron

SUBMITTER: Chia-Hsiang Chang  

LAB HEAD: Maxence V. Nachury

PROVIDER: PXD067892 | Pride | 2026-06-08

REPOSITORIES: Pride