Biology subjects

Chung, G. H.

Publications and source records attributed to Chung, G. H..

4 recordsLinked to original sources

bioRxiv2026

An early CYP26A1/CRYAA progenitor-glial domain marks the presumptive macular region during human retinal development

The human macula, a high-acuity retinal region essential for central vision, emerges early in development, but the cellular basis of its regional specialisation remains incompletely resolved. Building on recent studies that identified CYP26A1-mediated retinoic acid (RA) suppression in the presumptive macula, we define a CRYAA-positive progenitor-glial compartment in the temporal human retina from post-conception week (pcw) 7 onward. Single-cell RNA sequencing, immunohistochemistry and spatial morphometry indicate that this compartment is linked to regional gliogenic maturation and later corresponds to a specialised macular Muller glial population, rather than simply reflecting uniform pan-retinal developmental timing. Spatial mapping shows that the CYP26A1-positive domain remains delimited as the surrounding retina expands. Adult tissue analysis shows that CYP26A1 expression is retained in primate macular Muller glia and in corresponding acute-zone regions of visual-streak species. These findings extend current models of CYP26A1-mediated RA modulation in human acute zone/macular development by linking the early CYP26A1 domain to a regionally specialised CRYAA-positive progenitor-glial compartment. We propose that early macular patterning includes a spatially restricted glial programme that may contribute to later regional architecture and disease vulnerability.

developmental biology↗

bioRxiv2021

Tricalbin proteins regulate plasma membrane phospholipid homeostasis

The evolutionarily conserved extended synaptotagmin (E-Syt) proteins are calcium-activated lipid transfer proteins that function at contacts between the endoplasmic reticulum and plasma membrane (ER-PM contacts). However, roles of the E-Syt family members in PM lipid organisation remain unclear. Among the E-Syt family, the yeast tricalbin (Tcb) proteins are essential for PM integrity upon heat stress, but it is not known how they contribute to PM maintenance. Using quantitative lipidomics and microscopy, we find that the Tcb proteins regulate phosphatidylserine homeostasis at the PM. Moreover, upon heat-induced membrane stress, Tcb3 co-localises with the PM protein Sfk1 that is implicated in PM phospholipid asymmetry and integrity. The Tcb proteins also promote the recruitment of Pkh1, a stress-activated protein kinase required for PM integrity. Phosphatidylserine has evolutionarily conserved roles in PM organisation, integrity, and repair. We suggest that phospholipid regulation is an ancient essential function of E-Syt family members in PM integrity.

cell biology↗

bioRxiv2020

ER-PM contacts regulate apical domain formation in hepatocytes

Apico-basal membrane polarity is fundamental for epithelial cell development and function. Polarity factors including the small GTPase Cdc42, the Par3/Par6/aPKC complex, and cytoskeletal proteins are recruited by the anionic lipids phosphatidylinositol 4,5-bisphosphate and phosphatidylserine. But how these lipids accumulate at polarised sites remains unclear. We have examined roles of contacts between the endoplasmic reticulum and plasma membrane (ER-PM contacts) in generating lipid gradients during apical domain formation. Comprehensive electron microscopy analyses in hepatocytes and epithelial spheroids revealed two distinct ER-PM contact architectures that are spatially linked to apical and baso-lateral domains. Moreover, apical domain formation was delayed in HepG2 cells upon modulating the ER-PM contact proteins E-Syt1 and ORP5. We propose ER-PM contacts regulate apico-basal polarity via the lipid transfer proteins E-Syt1 and ORP5. Importantly, our findings suggest that the spatial organisation of ER-PM contacts is a conserved feature of polarised epithelial cells.

cell biology↗

bioRxiv2018

A Cytoplasmic GOLD Protein Controls Cell Polarity

Phosphoinositide lipids provide spatial landmarks during polarized secretion. Here, we elucidate a role for phosphatidylinositol 4-phosphate (PI4P) metabolism in the control of cell polarity. In budding yeast, PI4P is enriched at the plasma membrane of growing daughter cells. Upon heat shock however, PI4P rapidly increases at the plasma membrane in mother cells resulting in a more uniform PI4P distribution. Rather than phosphoinositide kinase activation, PI4P hydrolysis is impaired to generate the heat-induced PI4P signal in mother cells. This fine tune control of PI4P metabolism is mediated through attenuation of the Osh3 protein that binds and presents PI4P to a phosphoinositide phosphatase. Importantly, Osh3 undergoes phase transitions upon environmental stress conditions, resulting in intracellular aggregates and reduced cortical localization. The chaperone Hsp104 co-assembles with intracellular Osh3 granules, but is not required for their formation. Interestingly, the Osh3 GOLD domain, also present in the ER-localized p24 cargo adaptor family, is sufficient to form stress granules. Accordingly, GOLD-mediated phase transitions may provide a general mechanism to modulate secretion and growth upon transient changes in physiological and environmental conditions.

cell biology↗