A Purkinje cell specific GoLoco domain protein, L7/Pcp-2, modulates receptor-mediated inhibition of Cav2.1 Ca2+ channels in a dose-dependent manner.

摘要: Abstract L7/Pcp-2 is a GoLoco domain protein encoded by Purkinje cell dendritic mRNA. Although biochemical interactions of proteins with Gα o and i are well documented, little known about effector function modulation resulting from these interactions. The P-type Ca 2+ channels might be physiological effectors L7 because (1) they the major voltage-dependent (VDCC) that modulate output (2) regulated G i/o proteins. As first step towards validating this hypothesis to further understand possible effect its two isoforms, we have coexpressed v 2.1 κ-opioid receptors (KORs) varying amounts L7A or L7B in Xenopus oocytes measured ionic currents two-electrode voltage clamping. Without receptor activation did not alter channel activity. With tonic weak receptors, however, were inhibited 40–50%. This inhibition was enhanced low, but dampened high, expression levels differences observed between isoforms. enhancing occluded overexpression Gβγ, whereas disinhibition antagonized . We propose differentially affects Gβγ arms receptor-induced signaling concentration-dependent manner, through which it increases dynamic range regulation P/Q-type protein-coupled receptors. provides framework for designing experiments determine how local fluctuations influence signal processing cells.