Cho, I.-T. | bioRxiv Science

bioRxiv2020

Identification of select G-protein coupled receptors as regulators of the ER-mitochondria contact by drug screening

Interactions between the endoplasmic reticulum (ER) and mitochondria (Mito) are crucial for many cellular functions, and their interaction levels change dynamically depending on the cellular environment. Little is known about how the interactions between these organelles are regulated within the cell. Here we screened a compound library to identify chemical modulators for ER-Mito contacts. Multiple agonists of G-protein coupled receptors (GPCRs), beta-adrenergic receptors ({beta}-ARs) in particular, scored in this screen. Analyses in multiple orthogonal assays validated that GPCR activation promotes physical and functional interactions between the two organelles. Furthermore, we have elucidated potential downstream effectors mediating GPCR-induced ER-Mito contacts. Given the role of GPCRs in sensing various extracellular signals and subsequently eliciting appropriate cellular responses, our data provide significant insights into the roles of ER-Mito contacts in maintaining cellular homeostasis and in responding to physiological demands or stresses.

cell biology↗

bioRxiv2019

Organogenesis and Distribution of the Ocular Lymphatic Vessels in the Anterior Eye: Implication to Glaucoma Surgery Site Selection

Glaucoma surgeries, such as trabeculectomy, are performed to lower the intraocular pressure to reduce the risk of vision loss. The surgeries create a new passage in the eye that reroutes the aqueous humor outflow to the subconjunctival space, where the fluid is presumably absorbed by the conjunctival lymphatics. However, the current knowledge of these ocular surface lymphatics remains limited. Here, we characterized the biology and function of the ocular lymphatics using transgenic lymphatic reporter mice and rats. We found that the limbal and conjunctival lymphatic networks are progressively formed by a primary lymphatic vessel that grows out from the nasal-side medial canthus region at the time of birth. This primary lymphatic vessel immediately branches out and invades the limbus and conjunctiva, and then simultaneously encircles the cornea in a bidirectional manner. As a result, the distribution of the ocular lymphatic is significantly polarized toward the nasal side, and the limbal lymphatics are directly connected to the conjunctival lymphatics. New lymphatic spouts are mainly produced from the nasal-side limbal lymphatics, posing the nasal side of the eye more responsive to fluid drainage and inflammatory stimuli. Consistently, when a fluorescent tracer was injected, fluid clearance was much more efficient in the nasal side than the temporal side of the eyes. In comparison, blood vessels are evenly distributed on the front surface of the eyes. We found that these distinct vascular distribution patterns were also conserved in human eyes. Together, our study demonstrated that the ocular surface lymphatics are more densely present in the nasal side and uncovered the potential clinical benefits in selecting the nasal side as a surgical site for glaucoma surgeries to improve the fluid drainage.

developmental biology↗