Yang Hong Ph.D.

The long term goal of our lab is to elucidate the molecular and cellular mechanisms regulating the cell polarity under normal and diseases conditions (e.g. cancer and ischemia), using Drosophila, cultured cells and animal models.

A core set of a dozen or so “polarity proteins” play essential and conserved functions in regulating cell polarity in many different cell types. A fundamental process for establishing and maintaining cell polarity is the polarization of polarity proteins to mutually exclusive plasma membrane (PM)/cortical domains. Our current research focuses on how electrostatic interaction between plasma membrane (PM) and polarity proteins acts as a fundamental mechanism for establishing and maintaining cell polarity. We have identified multiple polarity proteins, including Lgl, aPKC and Dlg, as “polybasic polarity proteins” that contain previously unrecognized polybasic domains capable of electrostatically binding PM-enriched phospholipids such as PI4P and PIP2. Our research uncovered diverse mechanisms such as phosphorylation and allosteric conformation changes that control the biological functions and the mutually exclusive PM localizations of polarity protein complexes through regulating their electrostatic PM targeting.
 

[video: elife-79582-fig2-video2_S.mp4 ]

In addition, we discovered that electrostatic PM targeting of polybasic polarity proteins is highly susceptible to energetic stresses triggered by hypoxia, ATP inhibition and ischemia, which result in the acute and reversible depletion of PM PI4P and PIP2. Challenged by such dramatic energetic stress events, cells demonstrated remarkable resilience in the post-stress recovery of PM PI4P and PIP2, as well as the flawless PM retargeting of polybasic polarity proteins. Mechanisms underlying such cellular resilience presently remain unknown and is an active research topic in the lab.