Proteolytic cleavage of the voltage - gated Ca 2 + channel subunit : α 2 δ structural and functional features
نویسنده
چکیده
By mediating depolarization-induced Ca influx high voltage-activated (HVA) Ca channels control a variety of cellular events. 2+ 2+ These heteromultimeric proteins are composed of an ion-conducting ( ) and three auxiliary ( , and ) subunits. The subunit α1 α2δ β γ α2δ enhances the trafficking of the channel complex to the cell surface and increases channel open probability. To exert these effects, α2δ must undergo important post-translational modifications including a proteolytic cleavage that separates the extracellular from its α2 transmembrane domain. After this proteolysis both domains remain linked by disulfide bonds. In spite of its central role in δ determining the final conformation of the fully mature almost nothing is known about the physiological implications of this α2δ structural modification. In the current report, by using site-directed mutagenesis, the proteolytic site of was mapped to amino α2δ acid residues Arg-941 and Val-946. Substitution of these residues renders the protein insensitive to proteolytic cleavage as evidenced by the lack of molecular weight shift upon treatment with a disulfide reducing agent. Interestingly, these mutations significantly decreased whole-cell patch clamp currents without affecting the voltage-dependence or kinetics of the channels, suggesting a reduction in the number of channels targeted to the plasma membrane. MESH
منابع مشابه
Proteolytic cleavage of the voltage - gated Ca 2 + channel α 2 δ subunit : structural and functional features
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Proteolytic cleavage of the voltage-gated Ca2+ channel alpha2delta subunit: structural and functional features.
By mediating depolarization-induced Ca(2+) influx, high-voltage-activated Ca(2+) channels control a variety of cellular events. These heteromultimeric proteins are composed of an ion-conducting (alpha(1)) and three auxiliary (alpha(2)delta, beta and gamma) subunits. The alpha(2)delta subunit enhances the trafficking of the channel complex to the cell surface and increases channel open probabili...
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