Disturbed vesicular trafficking of membrane proteins in prion disease

Area of Science:

• Neuroscience
• Cell Biology
• Pathology

Background:

• The pathogenic mechanisms underlying prion diseases are not fully understood.
• Prion infections are known to disrupt cellular processes, but the specific molecular pathways involved require elucidation.

Purpose of the Study:

• To investigate the role of post-Golgi trafficking in prion disease pathogenesis.
• To determine if impaired membrane protein surface expression is a common feature of prion diseases.

Main Methods:

• Analysis of membrane protein trafficking in prion-infected mouse models.
• Localization studies of prions and pathogenic prion proteins within cellular compartments.
• Comparison of trafficking defects in acquired and hereditary prion disease models.

Main Results:

• Prion infection impairs post-Golgi trafficking of membrane proteins, reducing their surface expression.
• Reduced surface expression of membrane proteins occurs before the onset of clinical symptoms in prion-infected mice.
• Prions accumulate in endosomal compartments, particularly recycling endosomes, disrupting protein transport pathways.
• Impaired delivery of membrane proteins to the cell surface is observed in both acquired and hereditary prion disease models.

Conclusions:

• Prions may cause neuronal dysfunction and loss by disturbing post-Golgi membrane protein trafficking through accumulation in recycling endosomes.
• Impaired delivery of membrane proteins to the cell surface is a shared pathogenic event in acquired and hereditary prion diseases.