International Journal of Cell Biology / 2013 / Article / Fig 5

Review Article

Synaptic Dysfunction in Prion Diseases: A Trafficking Problem?

Figure 5

Theoretical model for how intracellular retention could perturb -dependent signaling. (a) acts as scaffold molecules that keep a prosurvival signaling complex in lipid rafts of the plasma membrane (PM). The lipid raft localization would be essential to activate neuroprotective signaling. (b) Owing to retention in transport organelles (ER/Golgi), function is lost and the signaling complex localizes in nonraft regions of the PM, losing its neuroprotective activity and potentially eliciting a neurotoxic signal. (c) Misfolded PrP sequesters the signaling module in intracellular compartments, leading to loss of neuroprotective function on the cell membrane. Intracellular retention might also cause the complex to function abnormally and generate a toxic signal.