https://scholar.dgist.ac.kr/handle/20.500.11750/730 2026-04-04T13:55:50Z 2026-04-04T13:55:50Z Kim, Byeol I Yeon, Jun-Hee Suh, Byung-Chang https://scholar.dgist.ac.kr/handle/20.500.11750/59928 2026-02-05T18:01:19Z 2025-09-30T15:00:00Z

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.

2025-09-30T15:00:00Z Jeong, Da-Jeong Woo, Jin-Nyeong Yun, Tery Baek, Myungin Suh, Byung-Chang https://scholar.dgist.ac.kr/handle/20.500.11750/59927 2026-02-05T18:01:18Z 2025-10-31T15:00:00Z

Title: Kv7 Channels as an Important Contributor to Alcohol-Induced Modulation of Neuronal Excitability in Neonatal Rat Superior Cervical Ganglion Author(s): Jeong, Da-Jeong; Woo, Jin-Nyeong; Yun, Tery; Baek, Myungin; Suh, Byung-Chang Abstract: Normal alcohols (n-alcohols) exhibit contrasting effects on neuronal excitability; specifi- cally, ethanol enhances neuronal firing, while hexanol suppresses it. Both compounds are known to inhibit sodium currents, yet the mechanisms behind their differing effects remain unclear. Our previous studies demonstrated that Kv7 channels are modulated differently by alcohol chain length, prompting investigation into their role in these contrasting effects. We conducted whole-cell patch clamp recordings on neonatal (P5-P7) rat superior cervical ganglion neurons to assess alcohol impacts on action potential firing and ionic currents, utilizing tetrodotoxin (TTX), XE991, and retigabine (RTG). Ethanol (100 mM) increased action potential frequency, whereas hexanol (3 mM) decreased it, despite both inhibiting sodium currents by 12% and 45%, respectively. Notably, ethanol inhibited Kv7 currents by 16%, while hexanol enhanced them by 29%. TTX alone did not affect firing frequency until sodium current inhibition exceeded 76%, indicating moderate sodium channel blockade cannot fully explain the effects of alcohol. XE991 increased firing frequency and depo- larized the resting membrane potential, while retigabine produced opposite effects. The combination of TTX with Kv7 modulators replicated the effects observed with each alco- hol. These findings suggest Kv7 channel modulation plays an important role in the chain length-dependent effects of alcohol on neuronal excitability.

2025-10-31T15:00:00Z Kim, Jung-Eun Ko, Woori Jin, Siwoo Woo, Jin-Nyeong Jung, Yuna Bae, Inah Choe, Han Kyoung Seo, Daeha Hille, Bertil Suh, Byung-Chang https://scholar.dgist.ac.kr/handle/20.500.11750/58226 2025-07-25T02:43:03Z 2024-12-31T15:00:00Z

Title: Activation of TMEM16E scramblase induces ligand independent growth factor receptor signaling and macropinocytosis for membrane repair Author(s): Kim, Jung-Eun; Ko, Woori; Jin, Siwoo; Woo, Jin-Nyeong; Jung, Yuna; Bae, Inah; Choe, Han Kyoung; Seo, Daeha; Hille, Bertil; Suh, Byung-Chang Abstract: The calcium-dependent phospholipid scramblase TMEM16E mediates ion transport and lipid translocation across the plasma membrane. TMEM16E also contributes to protection of membrane structure by facilitating cellular repair signaling. Our research reveals that TMEM16E activation promotes macropinocytosis, essential for maintaining plasma membrane integrity. This scramblase externalizes phosphatidylserine, typically linked to resting growth factor receptors. We demonstrate that TMEM16E can interact with and signal through growth factor receptors, including epidermal growth factor receptor, even without ligands. This interaction stimulates downstream phosphoinositide 3-kinase and facilitates macropinocytosis and internalization of annexin V bound to the membrane, a process sensitive to amiloride inhibition. Although TMEM16E is internalized during this process, it returns to the plasma membrane. TMEM16E- driven macropinocytosis is proposed to restore membrane integrity after perturbation, potentially explaining pathologies in conditions like muscular dystrophies, where TMEM16E functionality is compromised, highlighting its critical role in muscle cell survival.

2024-12-31T15:00:00Z Ko, Woori Lee, Euna Kim, Jung-Eun Lim, Hyun-Ho Suh, Byung-Chang https://scholar.dgist.ac.kr/handle/20.500.11750/57384 2025-07-25T03:38:31Z 2024-07-31T15:00:00Z

Title: The plasma membrane inner leaflet PI(4,5)P2 is essential for the activation of proton-activated chloride channels Author(s): Ko, Woori; Lee, Euna; Kim, Jung-Eun; Lim, Hyun-Ho; Suh, Byung-Chang Abstract: Proton-activated chloride (PAC) channels, ubiquitously expressed in tissues, regulate intracellular Cl- levels and cell death following acidosis. However, molecular mechanisms and signaling pathways involved in PAC channel modulation are largely unknown. Herein, we determine that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] of the plasma membrane inner leaflet is essential for the proton activation of PAC channels. PI(4,5)P2 depletion by activating phosphatidylinositol 5-phosphatases or Gq protein-coupled muscarinic receptors substantially inhibits human PAC currents. In excised inside-out patches, PI(4,5)P2 application to the cytoplasmic side increases the currents. Structural simulation reveals that the putative PI(4,5)P2-binding site is localized within the cytosol in resting state but shifts to the cell membrane’s inner surface in an activated state and interacts with inner leaflet PI(4,5)P2. Alanine neutralization of basic residues near the membrane-cytosol interface of the transmembrane helice 2 significantly attenuates PAC currents. Overall, our study uncovers a modulatory mechanism of PAC channel through inner membrane PI(4,5)P2. © The Author(s) 2024.

2024-07-31T15:00:00Z