TY - JOUR T1 - Biased Signaling: Distinct Ligand-directed Plasma Membrane Signalosomes Using a Common RGS/ G protein Core JF - bioRxiv DO - 10.1101/666578 SP - 666578 AU - Timothy J. Ross-Elliott AU - Justin Watkins AU - Xiaoyi Shan AU - Fei Lou AU - Bernd Dreyer AU - Meral Tunc-Ozdemir AU - Haiyan Jia AU - Jing Yang AU - Luguang Wu AU - Yuri Trusov AU - Patrick Krysan AU - Alan M. Jones Y1 - 2019/01/01 UR - http://biorxiv.org/content/early/2019/06/11/666578.abstract N2 - Biased signaling occurs when different ligands that are directed at the same receptor launch different cellular outcomes. Because of their pharmacological importance, we know the most about biased ligands and little is known about other mechanisms to achieve signaling bias. In the canonical animal G protein system, endocytosis of a 7-transmembrane GPCR desensitizes a cell from an extracellular signal. β-arrestins facilitate GPCR endocytosis but also propagates cytoplasmic signaling depending on the bias. In Arabidopsis, GPCRs are not required for G protein coupled signaling because the heterotrimeric G protein complex spontaneously exchanges nucleotide. Instead, the prototype 7-transmembrane Regulator of G Signaling 1 protein AtRGS1 modulates G signaling and through ligand-dependent endocytosis, de-repression of signaling is initiated but canonical arrestins are not involved. Endocytosis initiates from two separate pools of plasma membrane: microdomains and a clathrin-accessible neighborhood, each with a select set of discriminators, activators, and newly-discovered arrestin-like adaptors. Different trafficking origins and trajectories lead to different cellular outcomes. Thus, compartmentation with its attendant signalosome architecture is a previously unknown mechanism to drive biased signaling. ER -