A postsynaptic PI3K-cII dependent signaling controller for presynaptic homeostatic plasticity
Anna G Hauswirth,
Kevin J Ford,
Tingting Wang,
Richard D Fetter,
Amy Tong,
Graeme W Davis
Affiliations
Anna G Hauswirth
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Kevin J Ford
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Tingting Wang
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Richard D Fetter
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Amy Tong
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, United States; Kavli Institute for Fundamental Neuroscience, University of California, San Francisco, San Francisco, United States
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.
