biostudies-literatureMuller CSAustrian Science Fund FWF14950-7https://www.ebi.ac.uk/biostudies/studies/S-EPMC2930569biostudies-literatureUnknown107(34)Local Ca(2+) signaling occurring within nanometers of voltage-gated Ca(2+) (Cav) channels is crucial for CNS function, yet the molecular composition of Cav channel nano-environments is largely unresolved. Here, we used a proteomic strategy combining knockout-controlled multiepitope affinity purifications with high-resolution quantitative MS for comprehensive analysis of the molecular nano-environments of the Cav2 channel family in the whole rodent brain. The analysis shows that Cav2 channels, composed of pore-forming alpha1 and auxiliary beta subunits, are embedded into protein networks that may be assembled from a pool of approximately 200 proteins with distinct abundance, stability of assembly, and preference for the three Cav2 subtypes. The majority of these proteins have not previouslyProceedings of the National Academy of Sciences of the United States of AmericaQuantitative proteomics of the Cav2 channel nano-environments in the mammalian brain.PMC2930569P 20670Knaus HGSchindler JMuller CSStriessnig JFlockerzi VRammner BHaupt ABildl WFakler BMeissner MSchulte UfalseQuantitative proteomics of the Cav2 channel nano-environments in the mammalian brain.Local Ca(2+) signaling occurring within nanometers of voltage-gated Ca(2+) (Cav) channels is crucial for CNS function, yet the molecular composition of Cav channel nano-environments is largely unresolved. Here, we used a proteomic strategy combining knockout-controlled multiepitope affinity purifications with high-resolution quantitative MS for comprehensive analysis of the molecular nano-environments of the Cav2 channel family in the whole rodent brain. The analysis shows that Cav2 channels, composed of pore-forming alpha1 and auxiliary beta subunits, are embedded into protein networks that may be assembled from a pool of approximately 200 proteins with distinct abundance, stability of assembly, and preference for the three Cav2 subtypes. The majority of these proteins have not previously2010-01-01T00:00:00Z2010 Aug2025-07-24T03:04:43.53Z2025-07-24T03:04:43.53ZS-EPMC29305692066823610.1073/pnas.1005940107