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Fig. 3 | BMC Biology

Fig. 3

From: The biological function of the cellular prion protein: an update

Fig. 3

Schematic overview of possible physiological functions of PrPC and their effect in the central nervous system. PrPC regulates ion channels and neurotransmitter receptors at the pre- and postsynaptic levels. a PrPC might modulate VGCC trafficking at the presynapse via interaction with the α2δ-1 VGCC subunit. b Postsynaptically, PrPC dampens NMDA receptor-mediated currents by modulating various receptor subunits of this channel. It was speculated that control of NMDA receptor function might be related to certain reported phenotypes of PrPC-ablated mice. c PrPC may also control the glutamatergic system by modulating the subunit composition of kainate receptors. This possibly relates to increased susceptibility of PrPC-ablated mice to kainate-induced seizures. d PrPC associates with, and promotes cell surface localization of, AMPA receptor subunits. This facilitates zinc uptake at the synaptic cleft via AMPA receptors. On astrocytes, a PrPC–AMPA complex may be involved in the uptake of lactate. e PrPC binds to toxic oligomeric protein species. PrPC binds to Aβ oligomers and, in complex with metabotropic glutamate receptor 5 (mGluR5), was proposed to trigger intracellular signaling related to Alzheimer's disease pathology. f PrPC controls calcium influx via interaction with different ion channels. Additionally, PrPC was claimed to regulate calcium storage via the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA). g PrPC positively modulates potassium currents as exemplified by association with DPP6, an auxiliary subunit of the Kv 4.2 potassium channel. Control of calcium and potassium channels might be related to the alleged function of PrPC in neuronal excitability. ER endoplasmic reticulum

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