1.
Optogenetics Sheds Light on Brown and Beige Adipocytes.
Abstract:
Excessive food intake leads to lipid accumulation in white adipose tissue, triggering inflammation, cellular stress, insulin resistance, and metabolic syndrome. In contrast, the dynamic energy expenditure and heat generation of brown and beige adipose tissue, driven by specialized mitochondria, render it an appealing candidate for therapeutic strategies aimed at addressing metabolic disorders. This review examines the therapeutic potential of brown and beige adipocytes for obesity and metabolic disorders, focusing on recent studies that employ optogenetics for thermogenesis control in these cells. The findings delve into the mechanisms underlying UCP1-dependent and UCP1-independent thermogenesis and how optogenetic approaches can be used to precisely modulate energy expenditure and induce thermogenesis. The convergence of adipocyte biology and optogenetics presents an exciting frontier in combating metabolic disorders and advancing our understanding of cellular regulation and energy balance.
2.
Optogenetic control of focal adhesion kinase signaling.
Abstract:
Focal adhesion kinase (FAK) integrates signaling from integrins, growth factor receptors and mechanical stress to control cell adhesion, motility, survival and proliferation. Here, we developed a single-component, photo-activatable FAK, termed optoFAK, by using blue light-induced oligomerization of cryptochrome 2 (CRY2) to activate FAK-CRY2 fusion proteins. OptoFAK functions uncoupled from physiological stimuli and activates downstream signaling rapidly and reversibly upon blue light exposure. OptoFAK stimulates SRC creating a positive feedback loop on FAK activation, facilitating phosphorylation of paxillin and p130Cas in adherent cells. In detached cells or in mechanically stressed adherent cells, optoFAK is autophosphorylated upon exposure to blue light, however, downstream signaling is hampered indicating that the accessibility to these substrates is disturbed. OptoFAK may prove to be a useful tool to study the biological function of FAK in growth factor and integrin signaling, tension-mediated focal adhesion maturation or anoikis and could additionally serve as test system for kinase inhibitors.
