Curated Optogenetic Publication Database

Search precisely and efficiently by using the advantage of the hand-assigned publication tags that allow you to search for papers involving a specific trait, e.g. a particular optogenetic switch or a host organism.

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Spatiotemporal dynamics of membrane surface charge regulates cell polarity and migration.

blue CRY2/CIB1 D. discoideum RAW264.7 Control of cytoskeleton / cell motility / cell shape
bioRxiv, 20 May 2022 DOI: 10.1101/2022.05.19.492577 Link to full text
Abstract: During cell migration and polarization, hundreds of signal transduction and cytoskeletal components self-organize to generate localized protrusions. Although biochemical and genetic analyses have delineated many specific interactions, how the activation and localization of so many different molecules are spatiotemporally orchestrated at the subcellular level has remained unclear. Here we show that the regulation of negative surface charge on the inner leaflet of the plasma membrane plays an integrative role in the molecular interactions. Surface charge, or zeta potential, is transiently lowered at new protrusions and within cortical waves of Ras/PI3K/TORC2/F-actin network activation. Rapid alterations of inner leaflet anionic phospholipids, such as PI(4,5)P2, PI(3,4)P2, phosphatidylserine, and phosphatidic acid, collectively contribute to the surface charge changes. Abruptly reducing the surface charge by recruiting positively charged optogenetic actuators was sufficient to trigger the entire biochemical network, initiate de novo protrusions, and abrogate pre-existing polarity. These effects were blocked by genetic or pharmacological inhibitions of key signaling components such as Akt and PI3K/TORC2. Conversely, increasing the negative surface deactivated the network and locally suppressed chemoattractant-induced protrusions or subverted EGF-induced ERK activation. Computational simulations involving excitable biochemical networks demonstrated that slight changes in feedback loops, induced by recruitment of the actuators, could lead to outsized effects on system activation. We propose that key signaling network components act on, and are in turn acted upon, by surface charge, closing feedback loops which bring about the global-scale molecular self-organization required for spontaneous protrusion formation, cell migration, and polarity establishment.
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