Biophysical Society Conference | Tahoe 2022

Molecular Biophysics of Membranes

Monday Speaker Abstracts

DYNAMIC REMODELING OF HOST MEMBRANES BY SELF-ORGANIZING BACTERIAL EFFECTORS Ting-Sung Hsieh 1 ; Victor A Lopez 1 ; Miles H Black 1 ; Beatrice Ramm 2 ; Adam Osinski 1 ; Krzysztof Pawlowski 1,3 ; Diana R Tomchick 4,5 ; Jen Liou 6 ; Vincent S Tagliabracci 1,7 ; 1 UT Southwestern Medical Center, Department of Molecular Biology, Dallas, TX, USA 2 Princeton University, Department of Physics, Princeton, NJ, USA 3 Warsaw University of Life Sciences, Department of Biochemistry and Microbiology, Institute of Biology, Warsaw, Poland 4 UT Southwestern Medical Center, Department of Biophysics, Dallas, TX, USA 5 UT Southwestern Medical Center, Department of Biochemistry, Dallas, TX, USA 6 UT Southwestern Medical Center, Department of Physiology, Dallas, TX, USA 7 UT Southwestern Medical Center, Howard Hughes Medical Institute, Dallas, TX, USA A central theme in cell regulation is phosphorylation and dephosphorylation reactions catalyzed by competing kinases and phosphatases. Particularly, phosphoinositide kinases and phosphatases convert phosphatidylinositol (PI) into various phosphoinositide species that exhibit distinct, dynamic membrane localization to shape compartmental identity and regulate membrane trafficking in eukaryotic cells. Although spatiotemporal regulation of phosphoinositides has been widely studied, it is unclear if phosphoinositide kinases and phosphatases can operate in a self- organized manner to establish order and form structures on the membrane. Here we report a self- organizing system consisting of a bacterial phosphoinositide kinase and its opposing phosphatase that form spatiotemporal patterns, including traveling waves, to remodel host cellular membranes. The Legionella effector MavQ, a PI 3-kinase, is targeted to the host cell’s endoplasmic reticulum (ER). MavQ and the Legionella PI 3-phosphatase SidP, even in the absence of other bacterial components, drive rapid PI 3-phosphate turnover on the ER and spontaneously form traveling waves that spread along ER subdomains and induce vesicle/tubule budding. Evidence from in vitro reconstitution strongly suggests that a Turing-like reaction– diffusion mechanism accounts for the behavior of the MavQ/SidP system. Our results not only exemplify the importance of self-organizing behaviors that result from chemically interacting kinases and phosphatases in complex cellular behaviors but also reveal a mechanism that intracellular bacterial pathogens use to remodel host cellular membranes for survival.

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