The brain interactome of a permissive prion replication substrate.

Area of Science:

• Neuroscience
• Biochemistry
• Prion Biology

Background:

• Bank voles exhibit broad susceptibility to diverse prion strains.
• The molecular basis for bank vole prion protein (BVPrP) acting as a universal prion acceptor is not fully understood.
• Cell surface molecular environments and protein interactions may influence BVPrP's unique prion acceptance.

Purpose of the Study:

• To investigate the molecular environment and protein interactions of bank vole prion protein (BVPrP) in vivo.
• To compare the interactome of BVPrP with that of mouse prion protein (MoPrP).
• To determine if differential protein interactions explain BVPrP's universal prion acceptor properties.

Main Methods:

• Generation of knock-in mice expressing physiological levels of BVPrP (M109 isoform).
• Utilized mass spectrometry to compare the interactomes of BVPrP and MoPrP.
• Employed mild in vivo crosslinking of brain tissue for interactome analysis.

Main Results:

• Identified substantial overlap in the top interactors for both BVPrP and MoPrP.
• Established prion protein interactors, including neural cell adhesion molecules, Na+/K+-ATPase subunits, and contactin-1, were equally present in both interactomes.
• Demonstrated similar molecular environments for BVPrP and MoPrP within the mouse brain.

Conclusions:

• The molecular environments of BVPrP and MoPrP in mouse brains are largely similar.
• Differential protein interactions are unlikely to be the primary mechanism behind BVPrP's universal prion acceptor capabilities.
• Further research is needed to elucidate the precise mechanisms underlying BVPrP's broad prion susceptibility.