Direct, gabapentin-insensitive interaction of a soluble form of the calcium channel subunit α₂δ-1 with thrombospondin-4.

ABSTRACT: The α₂δ-1 subunit of voltage-gated calcium channels binds to gabapentin and pregabalin, mediating the analgesic action of these drugs against neuropathic pain. Extracellular matrix proteins from the thrombospondin (TSP) family have been identified as ligands of α₂δ-1 in the CNS. This interaction was found to be crucial for excitatory synaptogenesis and neuronal sensitisation which in turn can be inhibited by gabapentin, suggesting a potential role in the pathogenesis of neuropathic pain. Here, we provide information on the biochemical properties of the direct TSP/α₂δ-1 interaction using an ELISA-style ligand binding assay. Our data reveal that full-length pentameric TSP-4, but neither TSP-5/COMP of the pentamer-forming subgroup B nor TSP-2 of the trimer-for

SUBMITTER: El-Awaad E 

PROVIDER: S-EPMC6838084 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature