Browsing by Author "Simms, Brett A"

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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.