RRC ID 57140
Author Hauswirth AG, Ford KJ, Wang T, Fetter RD, Tong A, Davis GW.
Title A postsynaptic PI3K-cII dependent signaling controller for presynaptic homeostatic plasticity.
Journal Elife
Abstract 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.
Volume 7
Published 2018-1-5
DOI 10.7554/eLife.31535
PII 31535
PMID 29303480
PMC PMC5773188
MeSH Animals Class II Phosphatidylinositol 3-Kinases / metabolism* Class III Phosphatidylinositol 3-Kinases / metabolism Drosophila Drosophila Proteins / metabolism Electrophysiological Phenomena Neuronal Plasticity* Phosphatidylinositol Phosphates / metabolism Presynaptic Terminals / physiology* Signal Transduction* rab GTP-Binding Proteins / metabolism
IF 7.551
Times Cited 11