https://scholar.dgist.ac.kr/handle/20.500.11750/730 Sat, 03 Oct 2026 23:10:23 GMT 2026-10-03T23:10:23Z 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. Sun, 31 May 2026 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/60886 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. Sun, 31 May 2026 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/60877 2026-05-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/60851 Title: Heat-and PIP2-dependent TRPM4 activity underlies mutually exclusive human diseases Author(s): Tian, Yuhua; Bae, Soohyeon; Wu, Xuesong; Rouen, Kyle C.; Hernández-Gonzalez, Adriana; Han, Yanxiao; Tekreeti, Abdullah Al; Vu, Simon; Chen, Irene; Li, Ellen; Vorobyov, Igor; Yarov-Yarovoy, Vladimir; Suh, Byung-Chang; Hwang, Samuel T.; Zheng, Jie Abstract: Temperature-sensitive transient receptor potential melastatin subfamily 4 (TRPM4) ion channels convert intracellular calcium increases into membrane depolarization, thereby linking these two powerful cellular signaling pathways in diverse physiological processes. TRPM4 mutations cause severe human hereditary cardiovascular and skin diseases; mysteriously, while these mutations are gain-of-function in nature, they affect the heart and the skin in a mutually exclusive manner. Here, we show that phosphatidylinositol 4,5-bisphosphate (PIP2) lipid is a required cofactor for TRPM4 activity by tightly regulating its calcium sensitivity. We detected two PIP2 binding sites and located the high-affinity site adjacent to the S4-S5 linker. We demonstrated that skin disease-associated TRPM4 mutations relieve the tight control of PIP2, resulting in elevated channel activity but only at the body surface temperature. In contrast, heart diseases are associated with mutations known to boost the number of channels, an effect we found to be annihilated by channel desensitization outside the body core. Indeed, dendritic cells from transgenic mice carrying a skin disease mutant exhibited elevated migration at 25-to-30 degrees C range compared to those from normal mice, but no difference was observed at 37 degrees C. These findings shed light on a molecular mechanism for dynamic regulation of cellular signaling in physiology and diseases. Tue, 31 Mar 2026 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/60851 2026-03-31T15:00:00Z https://scholar.dgist.ac.kr/handle/20.500.11750/59928 Title: Palmitoylation Code and Endosomal Sorting Regulate ABHD17A Plasma Membrane Targeting and Activity Author(s): Kim, Byeol I; Yeon, Jun-Hee; Suh, Byung-Chang Abstract: Protein S-palmitoylation is a reversible lipid modification that regulates various aspects of protein function, including membrane association, subcellular localization, trafficking, stability, and activity. The depalmitoylase ABHD17A removes palmitate from multiple substrates, but its cellular positioning and the role of its own palmitoylation in regulating its function remain unclear. This study identifies a palmitoylation code within the conserved N-terminal cysteine cluster of ABHD17A, which governs its intracellular distribution and plasma membrane (PM) targeting. N-terminal palmitoylation is essential for PM localization. Through the use of code-restricted mutants, we found that modifications in the middle region (C14, C15) are critical for PM targeting and catalytic activity, while modifications at the front (C10, C11) and rear (C18) influence endosomal routing and delivery to the PM. Alanine scanning revealed that adjacent hydrophobic residues, particularly L9 and F13, are crucial for initial engagement with endomembranes. Sequence analysis and mutagenesis identified two tyrosine-based YXX & Oslash; motifs within the alpha/beta hydrolase fold; disruption of the proximal motif (L115A) decreased surface abundance and redirected ABHD17A to autophagosomes, indicating a need for YXX & Oslash;-dependent endosomal sorting, likely at the trans-Golgi network. Biochemical assays demonstrated a continuum of acylation states influenced by the palmitoylation code. This requirement for the middle region was conserved in ABHD17B and ABHD17C. Overall, our findings suggest a stepwise mechanism for ABHD17A delivery to the PM, enabling its depalmitoylase activity on membrane-bound substrates. Tue, 30 Sep 2025 15:00:00 GMT https://scholar.dgist.ac.kr/handle/20.500.11750/59928 2025-09-30T15:00:00Z