https://scholar.dgist.ac.kr/handle/20.500.11750/265 2026-10-22T09:16:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/61016 Title: Symmetry-driven gating of TRPM8 by PIP2 and menthol Author(s): Kim, Sun-Hong; Hong, Chansik; Park, Hyunwoo; Ju, Youngchang; Hwang, Youngsoo; Kim, Jinhyeong; Ji, Sangho; Yu, Wookyung; So, Insuk; Lee, Hyung Ho Abstract: TRPM8, a cold-activated ion channel, enables mammals to sense cooling agents such as menthol. While PIP2 is essential for menthol-induced activation of TRPM8, the precise cooperative mechanism and the specific binding mode of menthol have remained elusive. Here, we present cryo-EM structures of mouse TRPM8 in diverse conformations, including a PIP2-induced two-fold symmetric intermediate and an icilin-bound open state. Our results reveal that PIP2 binding initiates a symmetry-breaking event, priming the channel for activation through a noncanonical intermediate states. The subsequent binding of cooling agonists promotes a transition back to four-fold symmetry. Notably, we find that menthol stabilizes the PIP2-bound state, thereby overcoming channel desensitization, while icilin, in concert with calcium, stabilizes a fully open conformation. Together, these structures illuminate a stepwise activation pathway involving distinct symmetry transitions and define the cooperative allosteric mechanism by which PIP2 and cooling agonists gate the channel. 2026-06-30T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/61011 Title: Distinct lateral hypothalamic GABAergic ensembles encode motivational salience and value-scaled consumption Author(s): Lee, Myungsun; Jung, Sieun; Kwon, JiSoo Jennifer; Kondaurova, Anna; Nam, Myungsun; Kim, Donguk; Hyun, Jung Ho; Kim, Sung-Yon Abstract: Motivated behaviors span an approach-avoidance axis. Vgat-expressing lateral hypothalamic GABAergic neurons (LHVgat neurons) regulate motivated behaviors, but how distinct ensembles represent motivationally significant stimuli and consummatory actions across homeostatic needs remains unclear. Using longitudinal two-photon Ca2+ imaging to track individual neurons across behavioral sessions, we identify two dissociable LHVgat ensembles. One responds to aversive thermal stimuli and food-associated cues, including inaccessible food and learned predictors, but not to a behaviorally neutral auditory tone that evokes pupil dilation, supporting motivational salience coding across aversive and appetitive contexts rather than reflecting arousal alone. A second ensemble is preferentially engaged during ingestion across eating and drinking. Food-cue responses vary across stimuli in a manner consistent with their relative appetitive value, and ingestion responses scale with hunger and nutrient concentration; GLP-1 receptor agonism attenuates both. These findings reveal a functional division between motivationally salient cue processing and value-scaled consummatory encoding in LHVgat circuits. 2026-09-30T15:00:00Z 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/20.500.11750/60961 Title: Somatostatin-induced modulation of microglial activity contributes to mitigating Alzheimer's disease pathology Author(s): Jung, Hyeji; Hyun, Gaeun; Kim, Seunghye; Jeon, Younghyeon; Han, Kyung Ah; Lee, Kea Joo; Ko, Jaewon; Um, Ji Won Abstract: Somatostatin (SST) is a neuropeptide widely expressed in the central nervous system, known to exert inhibitory effects through the activation of G protein-coupled somatostatin receptors (SSTRs). Although its synaptic and network-level functions have been implicated in various neurological disorders, the direct peptidergic actions of SST-particularly on microglia-remain poorly understood. Given that SST levels are reduced in Alzheimer's disease (AD) and that microglia predominantly express SSTR2, we hypothesized that SST modulates microglial function in both physiological and AD-related contexts. In this study, we demonstrate that SST treatment enhances phagocytic capacity and suppresses pro-inflammatory cytokine release in cultured microglia. Furthermore, SST overexpression in an AD mouse model reduced microglial density and amyloid-beta plaque burden and improved hippocampus-dependent cognitive performance, indicating a protective effect mediated through microglial modulation. Our findings reveal a previously unrecognized role of SST in regulating microglial behavior and highlight the therapeutic potential of targeting the SST-SSTR signaling axis in neuroinflammatory and neurodegenerative diseases. 2026-07-31T15:00:00Z