Die ß-Untereinheit spannungsabhängiger Kalziumkanäle als Kanalmodulator und Endozytose-Aktivator
Zusammenfassung der Projektergebnisse
Our grant proposal was aimed to understand the molecular events leading Cavß to switch from a modulator of calcium channel function to an activator of dynamin-mediated endocytosis. We were able to show that changes in the quaternary structure of Cavß constitute the functional switch from channel activator to internalizer. Such a mechanism emerged as a novel regulatory input for modulation of calcium currents mediated by HVA channels and partially explained the functional versatility of this protein. The multiplicity of functions supported by Cavß is also expanded by being target of multiple post-translational modifications. A separate goal of this proposal was to identify PTMs in Cavß that are involved in modulation of voltage-dependent inactivation of Cavα1. Although we failed to fully complete this aim, we did contribute to the understanding of how this subunit regulates VDI by identifying a new segment within the protein that modulates VDI and by discovering a new membrane-anchoring domain in one member of the Cavß family that suffices to slow-down VDI.
