Astrocyte-neuron subproteomes and obsessive-compulsive disorder mechanisms

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• Astrocytes and neurons are key brain cells with extensive interactions.
• Understanding their distinct proteomes is crucial for brain physiology and disease research.

Purpose of the Study:

• To identify and compare the proteomes of striatal astrocytes and neurons in vivo.
• To investigate astrocyte subproteomes and their roles in signaling and homeostasis.
• To explore the function of SAPAP3 in both cell types concerning obsessive-compulsive disorder (OCD) phenotypes.

Main Methods:

• Utilized cell-specific and subcompartment-specific proximity-dependent biotinylation.
• Analyzed cytosolic and plasma membrane compartments of astrocytes and neurons.
• Performed genetic rescue, behavioral analyses, and molecular assessments in an OCD mouse model.

Main Results:

• Defined protein-level differences in signaling machinery between astrocytes and neurons.
• Revealed distinct astrocyte subproteomes, particularly the enrichment of SAPAP3 in specific compartments.
• Demonstrated that both astrocytic and neuronal SAPAP3 contribute to OCD-like behaviors in mice.

Conclusions:

• Astrocytes and neurons exhibit unique proteomes and signaling pathways.
• Astrocyte subcompartments have specialized proteomes, with SAPAP3 regulating the actin cytoskeleton.
• Targeting both astrocytes and neurons may offer therapeutic potential for OCD and other brain disorders.