https://scholar.dgist.ac.kr/handle/20.500.11750/722 2026-11-05T07:43:32Z https://scholar.dgist.ac.kr/handle/20.500.11750/61045 Title: 실시간 Gq 단백질 주기 감응형 형광공명에너지전달 센서 및 이의 용도 Author(s): 김용석; 서병창 Abstract: 본 발명은 실시간 Gq 단백질 주기 감응형 형광공명에너지전달 센서 및 이의 용도에 관한 것이다. 본 발명에 따른 바이오센서의 FRET 현상에 기반한 형광 발광 강도의 비율 변화를 통해, 리간드의 결합에 따른 G 단백질 수용체의 활성 여부 및 세포내 하위경로의 활성을 실시간으로 확인할 수 있다. https://scholar.dgist.ac.kr/handle/20.500.11750/60967 Title: Structural rigidity of the I-II loop couples CaV β anchoring to CaV2.2 gating modes Author(s): Woo, Jin-Nyeong; Kim, Jung-Eun; Suh, Byung-Chang Abstract: The auxiliary beta subunits of voltage-gated Ca2+ (Ca-V) channels are fundamental regulators of channel gating and neuronal excitability. While the subcellular localization of beta subunits is known to influence current density and inactivation, the precise kinetic mechanism by which they differentially modulate channel opening and closing remains elusive. Here, we report a kinetic paradox in Ca(V)2.2 channels: membrane-anchored beta subunits decelerate current decay during depolarization yet accelerate tail deactivation upon repolarization, whereas cytosolic beta subunits promote rapid decay but prolong deactivation. Using quantitative kinetic analysis and Markov state modeling, we demonstrate that macroscopic current decay is not solely a monolithic irreversible inactivation process but a composite of irreversible inactivation and a reversible transition to a nonconducting state. We reveal that membrane-anchored beta subunits suppress the transition to this reversible nonconducting state, thereby maintaining the open state, while facilitating a rapid return from the nonconducting state to prevent kinetic trapping. Furthermore, by manipulating the linker length of beta subunits and engineering the I-II loop hinge region (R370), we identify that the physical proximity of the beta subunit to the plasma membrane, coupled with the structural rigidity of the I-II loop, acts as a mechanical determinant that governs this gating pathway selection. Our findings provide a unified gating model in which the beta subunit fine-tunes the dynamic equilibrium between conducting and nonconducting states via mechanical constraint on the channel complex, offering a comprehensive resolution to the distinct regulation of Ca(V)2.2 kinetics. 2026-06-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60886 Title: TMEM16E-mediated macropinocytosis promotes cell survival under acidic stress Author(s): Kim, Jung-Eun; Lee, Byoung-Cheol; Suh, Byung-Chang Abstract: TMEM16E is a transmembrane protein that functions both as a phospholipid scramblase and a non-selective ion channel, playing a critical role in cellular ion transport and membrane dynamics. Recent studies have shown that the TMEM16E scramblase also facilitates membrane internalization through macropinocytosis. This study investigates the effects of extracellular protons on TMEM16E's scrambling activity and subsequent macropinocytosis under acidic conditions, which are particularly relevant in pathophysiological contexts such as muscular dystrophies and cancers. Our results indicate that TMEM16E-induced macropinocytosis, as evidenced by the internalization of annexin V, is significantly enhanced in acidic environments (pH 5.5). However, the overall number of macropinosomes, assessed using 70 kDa dextran, remained unchanged despite variations in extracellular pH. This suggests that TMEM16E-mediated macropinocytosis operates independently of extracellular proton concentrations. Upon extracellular acidification, both TMEM16E scrambling activity and macropinocytosis were rapidly inhibited, leading to a swift decrease in intracellular Ca2+ levels compared to physiological conditions. Notably, intracellular Ca2+ was cleared more quickly in acidic environments, indicating a regulatory role for the proton-dependent Ca2+ clearance pathways. Using wound healing and MTS assays, we demonstrated that TMEM16E expression significantly enhances cell proliferation and survival under acidic conditions. Our findings underscore the importance of TMEM16E-mediated macropinocytosis in maintaining plasma membrane integrity and promoting cell survival, highlighting its role as a crucial signaling pathway in both physiological and pathological contexts. 2026-05-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60877 Title: TWIK-1 plays distinct roles in spinal and peripheral sensory circuits controlling mechanical sensitivity and neuropathic hypersensitivity Author(s): Seo Young Yang; Tery Yun; Yunjeong Lee; Jae Hyuk Jeon; Seojung Kim; Eun Yeong Lim; Junhee Park; Kim, Yong Geon; Jonghoon Jung; Woo, Jin-Nyeong; Yan Zhang; Hyeonwi Son; John Shannonhouse; Juhyun Kim; Eunsil Cho; Young Hoon Sung; Eun-Mi Hwang; Byung-Chang Suh; Pojeong Park; Mi-Ryoung Song; Myungin Baek; Jaekwang Lee; Yu Shin Kim; Jae-Yong Park; Hyosang Lee Abstract: Ion channels are essential for sensing somatic stimuli, and their dysregulation can cause chronic conditions such as neuropathic pain. Although the potassium channel Twik-1 has been linked to sensory processing, its specific roles in the somatosensory system under normal and disease conditions remain unclear. Here, we demonstrate that systemic deletion of Twik-1 selectively reduces innocuous tactile and noxious mechanosensation evoked by both static and dynamic mechanical stimuli and facilitates recovery from mechanical hypersensitivity after peripheral nerve injury. Conditional deletion of Twik-1 in spinal cord neurons, pan-inhibitory neurons, or spinal inhibitory interneurons consistently disrupts innocuous tactile and noxious mechanical sensitivity, while sparing responses to high-intensity mechanical stimulation as well as noxious heat and cold. Notably, these manipulations do not affect nerve injury-induced mechanical hypersensitivity. In contrast, selective deletion of Twik-1 in dorsal root ganglion (DRG) neurons preserves baseline somatosensory and nociceptive functions, including innocuous tactile and noxious mechanical sensitivity, but impairs the persistence of mechanical hypersensitivity after nerve injury. This reduction in hypersensitivity is accompanied by decreased aberrant excitability in injured DRG neurons and distinct transcriptional changes. Together, these results suggest that Twik-1 facilitates innocuous tactile and noxious mechanosensation through spinal inhibitory circuits under baseline conditions, while supporting the maintenance of neuropathic pain via its functions in primary sensory neurons. 2026-05-31T15:00:00Z