Biology subjects

Shin, H.-W.

Publications and source records attributed to Shin, H.-W..

4 recordsLinked to original sources

bioRxiv2024

Lipid flippases ATP9A and ATP9B form a complex and contribute to the secretory pathway from the Golgi apparatus

Type IV P-type ATPases (P4-ATPases) serve as lipid flippases, translocating membrane lipids from the exoplasmic (or luminal) leaflet to the cytoplasmic leaflet of lipid bilayers. In mammals, these P4-ATPases are localized to distinct subcellular compartments. ATP8A1 and ATP9A, both members of the P4-ATPase family, are involved in endosome-mediated membrane trafficking, although the roles of P4-ATPases in the secretory pathway remain to be clarified. ATP9A and ATP9B are located in the trans-Golgi network, with ATP9A also present in endosomal compartments. This study unveiled the overlapping roles of ATP9A and ATP9B in transporting VSVG from the Golgi to the plasma membrane within the secretory pathway. Furthermore, we demonstrated that the flippase activities of ATP9A and ATP9B were crucial for transport process. Notably, we discovered the formation of homomeric and/or heteromeric complexes between ATP9A and ATP9B. The existence of the heteromeric complex notably contributed to the retention of ATP9A in the Golgi. Therefore, ATP9A and ATP9B play a role in the secretory pathway from the Golgi to the plasma membrane, forming either homomeric or heteromeric complexes.

cell biology↗

bioRxiv2023

Novel phosphatidylinositol flippases contribute to phosphoinositide homeostasis in the plasma membrane

Phosphatidylinositol is a precursor of various phosphoinositides, which play crucial roles in intracellular signaling and membrane dynamics and have impact on diverse aspects of cell physiology. Phosphoinositide synthesis and turnover occur in the cytoplasmic leaflet of the organellar and plasma membranes. P4-ATPases (lipid flippases) are responsible for translocating membrane lipids from the exoplasmic (luminal) to the cytoplasmic leaflet, thereby regulating membrane asymmetry. However, the mechanism underlying phosphatidylinositol translocation across cellular membranes remains elusive. Here, we discovered that the phosphatidylcholine flippases ATP8B1, ATP8B2, and ATP10A can also translocate phosphatidylinositol at the plasma membrane. To explore the function of these phosphatidylinositol flippases, we used cells depleted of CDC50A, a protein necessary for P4-ATPase function. Upon activation of the Gq-coupled receptor, depletion of phosphatidylinositol 4,5-bisphosphate [PtdIns(4,5)P2] was accelerated in CDC50A knockout cells compared with control cells, suggesting a decrease in PtdIns4,5P2 levels within the plasma membrane of the knockout cells. These findings highlight the pivotal role of P4-ATPases in maintaining phosphoinositide homeostasis and suggest a mechanism for enrichment of phosphatidylinositol in the cytoplasmic leaflet of the plasma membrane.

cell biology↗

bioRxiv2020

Antibiotic-dependent relationships between nasal microbiome and secreted proteome in chronic rhinosinusitis and nasal polyps

BackgroundAntibiotics are commonly prescribed to treat chronic rhinosinusitis (CRS); however, the effects of antibiotics on the microbiome and secreted proteome remain unknown in regard to CRS. ObjectiveWe analyzed the effects of antibiotics on the nasal microbiome and secreted proteome in the context of CRS using multi-omic analysis. MethodsNasal secretions were collected from 29 control, 30 CRS patients without nasal polyps (CRSsNP), and 40 CRS patients with nasal polyps (CRSwNP). A total of 99 subjects were divided into two groups that included subjects who had taken antibiotics 3 months prior to sampling (ABX) and those who had not (NABX). We performed 16S rDNA sequence analyses and Orbitrap mass spectrometry-based proteomic analyses in data-independent acquisition (DIA) on the nasal secretions. Spearman correlation was used to assess the correlations between the nasal microbiome and secreted proteome. ResultsWe observed a strong association between the nasal microbiome and secreted proteome according to disease status. Antibiotic use reduced differences in the microbial community and secreted proteome according to disease status. Interestingly, in nasal polyp (NP) patients, antibiotics exhibited strong effects not only on the nasal microbiome and the secreted proteome but also on their associations. Additionally, their correlations were strengthened in subjects who had taken antibiotics. ConclusionIntegrative analyses revealed that the correlations between the microbiome and the secreted proteome could be altered and strengthened in subjects who used antibiotics. These findings provide novel insight into the effects of antibiotics on the nasal environment and the host responses in CRS.

microbiology↗

bioRxiv2018

Identification and characterization of yeast and human glycosphingolipid flippases

Lipid transport is an essential process with manifest importance to human health and disease. Phospholipid flippases (P4-ATPases) transport lipids across the membrane bilayer, and are involved in signal transduction, cell division, and vesicular transport. Mutations in flippase genes cause or contribute to a host of diseases such as cholestasis, neurological deficits, immunological dysfunction, and metabolic disease. Genome-wide association studies have shown that ATP10A and ATP10D variants are associated with an increased risk of diabetes, obesity, myocardial infarction, and atherosclerosis; and ATP10D SNPs are associated with elevated levels of glucosylceramide (GlcCer) in plasma from diverse European populations. Although sphingolipids are strong contributors to metabolic disease, little is known about how GlcCer is transported across cell membranes. We have identified an evolutionarily conserved clade of P4-ATPases from Saccharomyces cerevisiae (Dnf1, Dnf2), Schizosaccharomyces pombe (Dnf2), and Homo sapiens (ATP10A, ATP10D) that transport GlcCer. Further, we establish the structural determinants necessary for the specific recognition of this sphingolipid substrate. Our molecular observations clarify the relationship between these flippases and human disease, and have fundamental implications for membrane organization and sphingolipid homeostasis.

biochemistry↗