Age-related homeostatic midchannel proteolysis of neuronal L-type voltage-gated Ca²⁺ channels.

ABSTRACT: Neural circuitry and brain activity depend critically on proper function of voltage-gated calcium channels (VGCCs), whose activity must be tightly controlled. We show that the main body of the pore-forming α1 subunit of neuronal L-type VGCCs, Cav1.2, is proteolytically cleaved, resulting in Cav1.2 fragment channels that separate but remain on the plasma membrane. This "midchannel" proteolysis is regulated by channel activity, involves the Ca(2+)-dependent protease calpain and the ubiquitin-proteasome system, and causes attenuation and biophysical alterations of VGCC currents. Recombinant Cav1.2 fragment channels mimicking the products of midchannel proteolysis do not form active channels on their own but, when properly paired, produce currents with distinct biophysical properties. Midchann

SUBMITTER: Michailidis IE 

PROVIDER: S-EPMC4052215 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature