Dipeptidyl-peptidase-like proteins cast in a new role: Enabling scorpion toxin block of A-type K+ channels

摘要

Subthreshold-operating A-type K+ currents exhibiting rapid inactivation are major regulators of somatodendritc excitability and plasticity in the nervous system (Jerng et al. 2004; Maffie & Rudy, 2008). There is also compelling evidence indicating that the Kv4.2 and Kv4.3 pore-forming subunits are significant molecular correlates of these currents (Maffie & Rudy, 2008). Although these subunits can form functional homo- and heterotetrameric A-type K+ channels, they need essential partners to recapitulate their native phenotype and perform their functions (Maffie & Rudy, 2008). Two distinct ancillary subunits are confirmed components of the Kv4 channel complex in neurones, namely the K+ channel-interacting proteins (KChlPs) and dipeptidyl-peptidase-like proteins (DPPs) encoded by various genes (KChIPl-4, DPP6 and DPP 10), which generate diverse splice variants. Current structural models of the ternary Kv4 channel complex suggest a dodecameric structure, in which there is one KChIP and one DPP for every Kv4.2/Kv4.3 subunit in the pore-forming tetrameric channel (Covarrubias etal 2008).