A5087966363- Cellular transport and secretion
- Cystic Fibrosis Research Advances
- Endoplasmic Reticulum Stress and Disease
- Drug Transport and Resistance Mechanisms
- Autophagy in Disease and Therapy
- Lipid Membrane Structure and Behavior
- Adenosine and Purinergic Signaling
- Neonatal Respiratory Health Research
- Hepatitis B Virus Studies
- Vestibular and auditory disorders
- Pancreatic function and diabetes
- Neuroscience of respiration and sleep
- Mitochondrial Function and Pathology
- SARS-CoV-2 and COVID-19 Research
- Energy Harvesting in Wireless Networks
- Ear Surgery and Otitis Media
- Cleft Lip and Palate Research
- COVID-19 Clinical Research Studies
- Tracheal and airway disorders
- Energy and Environment Impacts
- Lipid metabolism and biosynthesis
- Lysosomal Storage Disorders Research
- Adipokines, Inflammation, and Metabolic Diseases
- Genetic and Kidney Cyst Diseases
- Genomics and Rare Diseases
Yonsei University
2014-2025
Severance Hospital
2022-2025
Induction of endoplasmic reticulum ( ER )‐to‐Golgi blockade or stress induces Golgi reassembly stacking protein GRASP )‐mediated, Golgi‐independent unconventional cell‐surface trafficking the folding‐deficient ΔF508 ‐cystic fibrosis transmembrane conductance regulator CFTR ). However, molecular mechanisms underlying this process remain elusive. Here, we show that phosphorylation‐dependent dissociation homotypic complexes and subsequent relocalization to play a critical role in secretion ....
The most common mutation in cystic fibrosis patients is a phenylalanine deletion at position 508 (ΔF508) the CFTR (cystic transmembrane conductance regulator) gene. This impairs cell-surface trafficking of CFTR. During cellular stress, core-glycosylated CFTRΔF508 transported to cell surface from endoplasmic reticulum (ER) via an unconventional route that bypasses Golgi. However, mechanisms for this secretory pathway are not well delineated. Here, we report components macroautophagy/autophagy...
CFTR is a transmembrane protein that reaches the cell surface via conventional Golgi mediated secretion pathway. Interestingly, ER-to-Golgi blockade or ER stress induces alternative GRASP-mediated, Golgi-bypassing unconventional trafficking of wild-type and disease-causing ΔF508-CFTR, which has folding defects. Here, we show Sec16A, key regulator transport, plays critical role in exit cargos during secretion. In an initial gene silencing screen, Sec16A knockdown abolished ΔF508-CFTR induced...
As an enveloped virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) delivers its viral genome into host cells via fusion of the and cell membranes. Here, we show that ANO6/TMEM16F-mediated surface exposure phosphatidylserine is critical for SARS-CoV-2 entry ANO6-selective inhibitors are effective against infections. Application Spike pseudotyped virus (SARS2-PsV) evokes a cytosolic Ca2+ elevation ANO6-dependent externalization in ACE2/TMPRSS2-positive mammalian cells. A...
Craniosynostosis (CRS) is characterized by the development of abnormal cranial suture ossification and premature fusion. Despite identification several associated genetic disorders, determinants CRS remain poorly understood. In this study, we conducted integrative analyses on 225 exomes, comprising 121 probands 104 parental exomes (52 trios). These encompassed de novo pathogenic variants, digenic combinations within haploinsufficient genes harboring rare variants. Our analysis unveils a...
Zinc finger MYND-type-containing 10 (ZMYND10), a cytoplasmic protein expressed in ciliated cells, causes primary ciliary dyskinesia (PCD) when mutated; however, its function is poorly understood. Therefore, this study, we examined the roles of ZMYND10 using Zmynd10–/–mice exhibiting typical PCD phenotypes, including hydrocephalus and laterality defects. In these mutants, morphology, number motile cilia, 9+2 axoneme structure were normal; inner outer dynein arms (IDA ODA, respectively)...
Abstract Under ER stress conditions, the form of transmembrane proteins can reach plasma membrane via a Golgi‐independent unconventional protein secretion (UPS) pathway. However, targeting mechanisms for UPS are unknown. Here, this study reports that TMED play critical role in stress‐associated proteins. The gene silencing results reveal TMED2, TMED3, TMED9 and TMED10 involved proteins, such as CFTR, pendrin SARS‐CoV‐2 Spike. Subsequent mechanistic analyses indicate TMED3 recognizes...
Abstract Multidrug resistance 3 (MDR3), encoded by the ATP-binding cassette, subfamily B, member 4 gene ( ABCB4 ), localizes to canalicular membrane of hepatocytes and translocates phosphatidylcholine from inner leaflet outer membrane. Progressive familial intrahepatic cholestasis type (PFIC3) is a rare hepatic disease caused genetic mutations . In this study, we characterized 8 found in PFIC3 patients, using vitro molecular assays. First, examined transport activity each mutant measuring...
The Golgi apparatus plays a central role in the intracellular transport of macromolecules. However, molecular mechanisms Golgi-mediated lipid remain poorly understood. Here, we show that genetic inactivation Golgi-resident protein GRASP55 mice reduces whole-body fat mass via impaired intestinal absorption and evokes resistance to high-fat diet induced body weight gain. Mechanistic analyses reveal participates droplet (LD) targeting some LD-associated lipases, such as ATGL MGL, which is...
Anti-tuberculosis (AT) medications, including isoniazid (INH), can cause drug-induced liver injury (DILI), but the underlying mechanism remains unclear. In this study, we aimed to identify genetic factors that may increase susceptibility of individuals AT-DILI and examine interactions lead (INH)-induced hepatotoxicity. We performed a targeted sequencing analysis 380 pharmacogenes in discovery cohort 112 patients (35 77 controls) receiving AT treatment for active tuberculosis....
Shank2 is a PDZ (PSD-95/discs large/ZO-1)-based adaptor that has been suggested to regulate membrane transporting proteins in the brain and epithelial tissues. Here, we report mutant (Shank2(-/-)) mice exhibit aberrant fluid ion transport intestine. Molecular characterization using tissues from Shank2(+/+) Shank2(-/-) revealed long spliceoform of (Shank2E) predominantly expressed pancreatic, renal intestinal epithelia. In functional assays, deletion increased cystic fibrosis transmembrane...
Cystic fibrosis (CF), caused by mutations in the cystic transmembrane conductance regulator (CFTR) gene, is rare among non-Caucasians. We aimed to identify clinical features and CFTR Korean children.We included 18 pediatric patients with CF diagnosed using sweat chloride test or genetic analysis for 30 years. HEK293 cells were transfected wild-type CFTR, ΔF508-CFTR, L441P-CFTR mutant plasmids 24 hours treated correctors (VX809 VX661).The median age at diagnosis was 9.2 Eleven had growth...
Secretory proteins, including plasma membrane are generally known to be transported the through endoplasmic reticulum- to-Golgi pathway. However, recent studies have revealed that several proteins and cytosolic lacking a signal peptide released via an unconventional protein secretion (UcPS) route, bypassing Golgi during their journey cell surface. For instance, transmembrane such as misfolded cystic fibrosis conductance regulator (CFTR) Spike of coronaviruses been observed reach surface UcPS...
Variants in SLC26A4 (pendrin) are the most common reasons for genetic hearing loss and vestibular dysfunction East Asians. In patients with Pendred syndrome DFNB4 (autosomal recessive type of 4), caused by variants SLC26A4, function is residual at birth deteriorates over several years, no curative treatment these disorders. present study, we revealed that a novel small molecule restores expression mutant pendrin. High-throughput screening 54,000 molecules was performed. We observed pendrin...
Most transmembrane proteins are conventionally transported through the endoplasmic reticulum to Golgi apparatus and then plasma membrane. Recently, some integral membrane have been found reach via unconventional protein secretion (UPS) pathways that bypass under certain conditions. However, mechanisms for this UPS still not fully delineated. Here, we report components of autophagic ESCRT involved in CFTR. In HEK293 HeLa cells, induction ER stress by thapsigargin or blockade ER-to-Golgi...