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Stac adaptor proteins regulate trafficking and function of muscle and neuronal L-type Ca 2+ channels

2014; National Academy of Sciences; Volume: 112; Issue: 2 Linguagem: Inglês

10.1073/pnas.1423113112

1091-6490

Alexander Polster, Stefano Perni, Hicham Bichraoui, Kurt G. Beam,

Neuroscience and Neuropharmacology Research

Significance Voltage-gated calcium channels are essential for diverse cellular functions. For example, Ca V 1.1 channels trigger skeletal muscle contraction and Ca V 1.2 channels regulate neural gene expression in response to neuronal activity. Thus, it is important to understand the cellular mechanisms that regulate delivery of these channels to the plasma membrane and that govern calcium movements via the membrane-inserted channels. Here we show that the cellular adapter protein “Stac3” participates in both processes. Specifically, Stac3 binds to both Ca V 1.1 and Ca V 1.2. This binding is essential for efficient delivery of Ca V 1.1 to the plasma membrane, but not for Ca V 1.2. However, binding of Stac3, or the related protein Stac2, to Ca V 1.2 causes a dramatic slowing of inactivation, thereby increasing calcium entry via Ca V 1.2.