성지혜 교수

Matrix mechanics controls cell fate by modulating the bonds between integrins and extracellular matrix (ECM) proteins. However, it remains unclear how fibronectin (FN), type 1 collagen, and their receptor integrin subtypes distinctly control force transmission to regulate focal adhesion kinase (FAK) activity, a crucial molecular signal governing cell adhesion/migration. Here we showed, using a genetically encoded FAK biosensor based on fluorescence resonance energy transfer, that FN-mediated FAK

Living cells are continuously exposed to mechanical cues, and can translate these signals into biochemical information (e.g. mechanotransduction). This process is crucial in many normal cellular functions, e.g. cell adhesion, migration, proliferation, and survival, as well as the progression of diseases such as cancer. Focal adhesions are the major sites of interactions between extracellular mechanical environments and intracellular biochemical signalling molecules/cytoskeleton, and hence focal

Genetically encoded biosensors based on fluorescent proteins (FPs) allow for the real-time monitoring of molecular dynamics in space and time, which are crucial for the proper functioning and regulation of complex cellular processes. Depending on the types of molecular events to be monitored, different sensing strategies need to be applied for the best design of FP-based biosensors. Here, we review genetically encoded biosensors based on FPs with various sensing strategies, for example, transloc

Optobiochemical control of protein activities allows the investigation of protein functions in living cells with high spatiotemporal resolution. Over the last two decades, numerous natural photosensory domains have been characterized and synthetic domains engineered and assembled into photoregulatory systems to control protein function with light. Here, we review the field of optobiochemistry, categorizing photosensory domains by chromophore, describing photoregulatory systems by mechanism of ac

These data demonstrate that complexation of IL-4 AS-ODNs with PEI provides a potential therapeutic tool in controlling inflammation associated with allergic asthma, and further presents an opportunity to the development of clinical therapy based on combination of multiple AS-ODNs of cytokines and/or signaling effectors involved in Th2 inflammation and eosinophilia.

Platelet-derived growth factor receptor (PDGFR) senses extracellular growth factors and transfer the signals inside the cells regulating cell proliferation, migration and survival. It has been controversial at which membrane microdomains PDGFRs reside and how they control such diverse intracellular signaling pathways. Here, we developed a novel PDGFR biosensor based on fluorescence resonance energy transfer (FRET), which can detect the real-time PDGFR activity in live cells with high spatiotempo

How protein signaling networks respond to different input strengths is an important but poorly understood problem in cell biology. For example, RhoA can promote focal adhesion (FA) growth or disassembly, but how RhoA activity mediates these opposite outcomes is not clear. Here, we develop a photoswitchable RhoA guanine nucleotide exchange factor (GEF), psRhoGEF, to precisely control endogenous RhoA activity. Using this optical tool, we discover that peak FA disassembly selectively occurs upon ac

G protein-coupled receptors (GPCRs) regulate a wide range of physiological and pathophysiological cellular processes, thus it is important to understand how GPCRs are activated and function in various cellular contexts. In particular, the activation process of GPCRs is dynamically regulated upon various extracellular stimuli, and emerging evidence suggests the subcellular functions of GPCRs at endosomes and other organelles. Therefore, precise monitoring of the GPCR activation process with high

Dopaminergic signaling is regulated by transient micromolar (phasic) and background nanomolar (tonic) dopamine releases in the brain. These dopamine signals can be differentially translated by dopamine receptor type 1 and type 2, DRD1 and DRD2, which are G protein-coupled receptors (GPCRs). In response to dopamine, DRD1 and DRD2 are known to mediate opposite functions on cAMP production via Gs and Gi protein signaling. Interestingly, they can form a heterodimer. However, receptor crosstalk betwe

The complex information-processing capabilities of the central nervous system emerge from intricate patterns of synaptic input-output relationships among various neuronal circuit components. Understanding these capabilities thus requires a precise description of the individual synapses that comprise neural networks. Recent advances in fluorescent protein engineering, along with developments in light-favoring tissue clearing and optical imaging techniques, have rendered light microscopy (LM) a po

Autophagy is an essential cellular process of self-degradation for dysfunctional or unnecessary cytosolic constituents and organelles. Dysregulation of autophagy is thus involved in various diseases such as neurodegenerative diseases. To investigate the complex process of autophagy, various biochemical, chemical assays, and imaging methods have been developed. Here we introduce various methods to study autophagy, in particular focusing on the review of designs, principles, and limitations of the

Rho GTPases play crucial roles in cell motility by regulation of actin cytoskeleton dynamics. For example, Cdc42 induces the formation of filopodia, and RhoA is involved in the assembly of actin stress fibers and cell contraction. While individual roles of RhoA and Cdc42 are well studied, cellular responses to combinations of RhoA and Cdc42 activity are poorly understood. Previous methods for investigating functions of multiple proteins, such as dominant-negative mutants or siRNA, may cause seco