Browsing by Author "Stys, Peter K"

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    A T-type channel-calmodulin complex triggers αCaMKII activation
    (2017-08-11) Asmara, Hadhimulya; Micu, Ileana; Rizwan, Arsalan P; Sahu, Giriraj; Simms, Brett A; Zhang, Fang-Xiong; Engbers, Jordan D T; Stys, Peter K; Zamponi, Gerald W; Turner, Ray W
    Abstract Calmodulin (CaM) is an important signaling molecule that regulates a vast array of cellular functions by activating second messengers involved in cell function and plasticity. Low voltage-activated calcium channels of the Cav3 family have the important role of mediating low threshold calcium influx, but were not believed to interact with CaM. We find a constitutive association between CaM and the Cav3.1 channel at rest that is lost through an activity-dependent and Cav3.1 calcium-dependent CaM dissociation. Moreover, Cav3 calcium influx is sufficient to activate αCaMKII in the cytoplasm in a manner that depends on an intact Cav3.1 C-terminus needed to support the CaM interaction. Our findings thus establish that T-type channel calcium influx invokes a novel dynamic interaction between CaM and Cav3.1 channels to trigger a signaling cascade that leads to αCaMKII activation.
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    Differential modulation of NMDA and AMPA receptors by cellular prion protein and copper ions
    (2018-10-25) Huang, Sun; Chen, Lina; Bladen, Chris; Stys, Peter K; Zamponi, Gerald W
    Abstract N-Methyl-D-aspartate receptors (NMDARs) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) are two major types of ionotropic glutamate receptors involved in synaptic transmission. However, excessive activity of these receptors can be cytotoxic and thus their function must be precisely controlled. We have previously reported that NMDA receptor activity is dysregulated following genetic knockout of cellular prion protein (PrPC), and that PrPC regulation of NMDA receptors is copper-dependent. Here, we employed electrophysiological methods to study NMDAR and AMPAR currents of cultured hippocampal neurons from PrPC overexpresser mice. We show that NMDA receptor current amplitude and kinetics are differentially modulated by overexpression of human or mouse PrPC. By contrast, AMPA receptor activity was unaffected. Nonetheless, AMPA receptor activity was modulated by copper ions in a manner similar to what we previously reported for NMDA receptors. Taken together, our findings reveal that AMPA and NMDA receptors are differentially regulated by PrPC, but share common modulation by copper ions.