FREQUENCY AND AMPLITUDE CONTROL OF CORTICAL OSCILLATIONS BY LIPID METABOLISM

Abstract

Dynamic patterns, such as oscillations and waves, of signaling factors are of great importance to cell physiology in single and multicellular systems. Currently, majority of the studies focus primarily on cytoskeleton-dependent feedbacks. In contrast, information on signaling mechanisms upstream of the actin cytoskeleton remains unclear.

In my study, I report phosphoinositides traveling waves on the plasma membrane of rat basophilic leukemia (RBL) mast cells (Xiong et al. 2016). Sequential waves of phosphoinositides are generated by two phase-shifted phosphoinositide phosphatases namely synaptojanin 2 and SHIP1. By perturbing phosphoinositides using optogenetic methods and chemical drugs, I demonstrate that the pulses of PtdIns(4,5)P2 regulate the amplitude of cyclic membrane waves while PtdIns(3,4)P2 sets the frequency. Class I PI3Kδ is the main functional PI3K involved in regulating the frequency through phosphatase-dependent inhibitory action. Besides, dynamic patterns of global oscillations have been observed on the plasma membrane and the ER membrane coupling with calcium oscillations.