TY - JOUR TI - A postsynaptic PI3K-cII dependent signaling controller for presynaptic homeostatic plasticity AU - Hauswirth, Anna G AU - Ford, Kevin J AU - Wang, Tingting AU - Fetter, Richard D AU - Tong, Amy AU - Davis, Graeme W A2 - Shen, Kang A2 - Marder, Eve VL - 7 PY - 2018 DA - 2018/01/05 SP - e31535 C1 - eLife 2018;7:e31535 DO - 10.7554/eLife.31535 UR - https://doi.org/10.7554/eLife.31535 AB - Presynaptic homeostatic plasticity stabilizes information transfer at synaptic connections in organisms ranging from insect to human. By analogy with principles of engineering and control theory, the molecular implementation of PHP is thought to require postsynaptic signaling modules that encode homeostatic sensors, a set point, and a controller that regulates transsynaptic negative feedback. The molecular basis for these postsynaptic, homeostatic signaling elements remains unknown. Here, an electrophysiology-based screen of the Drosophila kinome and phosphatome defines a postsynaptic signaling platform that includes a required function for PI3K-cII, PI3K-cIII and the small GTPase Rab11 during the rapid and sustained expression of PHP. We present evidence that PI3K-cII localizes to Golgi-derived, clathrin-positive vesicles and is necessary to generate an endosomal pool of PI(3)P that recruits Rab11 to recycling endosomal membranes. A morphologically distinct subdivision of this platform concentrates postsynaptically where we propose it functions as a homeostatic controller for retrograde, trans-synaptic signaling. KW - endosome KW - homeostatic plasticity KW - neurotransmission KW - systems biology KW - membrane trafficking KW - neuromuscular junction JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -