UC San Diego

Plasma membrane compartments known as functional microdomains, such as membrane lipid rafts (MLRs) and caveolae, are critical in maintaining membrane structure and function which ultimately influences cellular survival. Numerous studies demonstrate that membrane microdomains are necessary for vital cellular functions like intracellular transport and cell signaling; but it remains unclear how plasma membrane organization is determined, how membrane microdomains regulate membrane repair, and how they work with intracellular organelles to enhance function. To define the role of membrane microdomains in facilitating cellular resilience, we focus on three specific areas: 1) circadian control of membrane dynamics, 2) membrane microdomain regulation of membrane repair, and 3) membrane microdomain regulation of intracellular function. Our findings suggest that membrane structural dynamics follow a daily oscillatory pattern, and that membrane composition and organization may be partially determined by Bmal1 dependent clock genes. Moreover, we found that over-expression of caveolin, a structural protein critical to caveolae, enhances the efficiency of membrane repair. Lastly, we expect that over-expression of caveolin will improve mitochondrial function in upcoming studies. These studies suggest that caveolae improve cellular resilience by enhancing membrane durability and organelle function. Thus, these studies establish a holistic understanding of the plasma membrane and its microdomains, laying the groundwork for further research on oscillatory rhythms at the membrane level, quantification and enhancement of membrane repair kinetics, and optimization of mitochondrial and membrane function via manipulations of membrane composition.