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@ARTICLE{Castilla:1042352,
      author       = {Castilla, Francisco and Lugo, Victor and Miranda-Laferte,
                      Erick and Jordan, Nadine and Huesgen, Pitter F. and
                      Santiago-Schübel, Beatrix and Alfonso-Prieto, Mercedes and
                      Hidalgo, Patricia},
      title        = {{M}apping the interaction surface between {C}a{V}β and
                      actin and its role in calcium channel clearance},
      journal      = {Nature Communications},
      volume       = {16},
      number       = {1},
      issn         = {2041-1723},
      address      = {[London]},
      publisher    = {Springer Nature},
      reportid     = {FZJ-2025-02546},
      pages        = {4352},
      year         = {2025},
      abstract     = {Defective ion channel turnover and clearance of damaged
                      proteins are associated with aging and neurodegeneration.
                      The L-type CaV1.2 voltage-gated calcium channel mediates
                      depolarization-induced calcium signals in heart and brain.
                      Here, we determined the interaction surface between actin
                      and two calcium channel subunits, CaVβ2 and CaVβ4, using
                      cross-linking mass spectrometry and protein-protein docking,
                      and uncovered a role in replenishing conduction-defective
                      CaV1.2 channels. Computational and in vitro mutagenesis
                      identified hotspots in CaVβ that decreased the affinity for
                      actin but not for CaV1.2. When coexpressed with CaV1.2, none
                      of the tested actin-association-deficient CaVβ mutants
                      altered the single-channel properties or the total number of
                      channels at the cell surface. However, coexpression with the
                      CaVβ2 hotspot mutant downregulated current amplitudes, and
                      with a concomitant reduction in the number of functionally
                      available channels, indicating that current inhibition
                      resulted from a build-up of conduction silent channels. Our
                      findings established CaVβ2-actin interaction as a key
                      player for clearing the plasma membrane of corrupted CaV1.2
                      proteins to ensure the maintenance of a functional pool of
                      channels and proper calcium signal transduction. The
                      CaVβ-actin molecular model introduces a potentially
                      druggable protein-protein interface to intervene
                      CaV-mediated signaling processes.},
      cin          = {IBI-1 / IBI-7 / INM-9},
      ddc          = {500},
      cid          = {I:(DE-Juel1)IBI-1-20200312 / I:(DE-Juel1)IBI-7-20200312 /
                      I:(DE-Juel1)INM-9-20140121},
      pnm          = {5244 - Information Processing in Neuronal Networks
                      (POF4-524) / DFG project G:(GEPRIS)394431587 - FOR 2795:
                      Synapsen unter Stress: akute Veränderungen durch mangelnde
                      Energiezufuhr an glutamatergen Synapsen (394431587)},
      pid          = {G:(DE-HGF)POF4-5244 / G:(GEPRIS)394431587},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {40348749},
      UT           = {WOS:001501680700005},
      doi          = {10.1038/s41467-025-59548-x},
      url          = {https://juser.fz-juelich.de/record/1042352},
}