https://scholar.dgist.ac.kr/handle/20.500.11750/265 2026-09-29T22:21:50Z https://scholar.dgist.ac.kr/handle/20.500.11750/60905 Title: Translational Profiling of Drd2-Expressing Populations Reveals Molecular Heterogeneity of Dentate Gyrus Mossy Cells along the Dorsoventral Axis Author(s): Jeong, Minseok; Jang, Jin-Hyeok; Oh, Seo-Jin; Choi, Ji-Woong; Oh, Yong-Seok Abstract: Hilar mossy cells (MCs) are crucial for integrating and propagating signals across the hippocampal dorsoventral axis, mediating cognitive and affective processing. While MCs exhibit profound dorsoventral differences in their projections, physiology, and behavioral roles, the molecular basis underlying this functional specialization remains largely unexplored. To address this gap, we used translating ribosome affinity purification (TRAP) in male mice to systematically compare the translatome of Drd2-expressing, MC-enriched populations along the dorsoventral axis. This analysis revealed distinct translational signatures with 1,442 genes enriched in dorsal and 1,337 genes in ventral Drd2-expressing, MC-enriched populations. Pathway analysis demonstrated significant functional segregation along the dorsoventral axis. The dorsal population is notably enriched for genes linked to neuronal connectivity and synaptic transmission, whereas the ventral counterpart shows enrichment in genes associated with energy metabolism and cellular maintenance. Specifically, we identified a subset of dorsal enriched genes, including neurotransmitter receptors, ion channels, and axon guidance regulators, contrasting with ventral enriched genes highly related to glucose/fatty acid metabolism, oxidative phosphorylation, and exocytosis. We further predicted distinct sets of upstream transcriptional regulators activated in each subpopulation, providing insights into the regulatory networks that may drive molecular divergence. Our findings provide a translatomic basis for the dorsoventral heterogeneity of Drd2-expressing neurons that include MCs, offering molecular signatures associated with their differential contributions to hippocampal function. 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/20.500.11750/60885 Title: Voltage dynamics of cortical dendrites in vivo Author(s): Wong-Campos, J. David; Park, Pojeong; Lee, Byung Hun; Davis, Hunter C.; Qi, Yitong; Tian, He; Itkis, Daniel G.; Kim, Doyeon; Grimm, Jonathan B.; Plutkis, Sarah E.; Lavis, Luke D.; Cohen, Adam E. Abstract: Voltage dynamics in dendrites, which result both from integrating synaptic inputs and back-propagating action potentials (bAPs) from the soma, contribute to plasticity. Mapping these dynamics in the dendritic arbors of live animals is crucial for understanding neuronal computation and plasticity rules. Here we combine targeted channelrhodopsin activation with dual-plane structured illumination voltage imaging for simultaneous monitoring of dendritic and somatic voltage response dynamics in cortical layer 2/3 pyramidal neurons in anesthetized and awake mice. We examined the integration of synaptic inputs and compared the dynamics of optogenetically evoked, spontaneous and sensory-evoked subthreshold and bAP dynamics. Our measurements revealed a broadly correlated membrane voltage throughout the dendritic arbor and only weak signatures of electrical compartmentalization within individual dendritic branches. However, we observed strong spiking-history-dependent modulation of bAP propagation into distal dendrites. We propose that this dendritic filtering of bAPs may have a critical role in the regulation of bursting and in activity-dependent plasticity. 2026-07-31T15:00:00Z 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