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bioRxiv2018

Rac1 Activated by DOCK1 in Combination with Rab31 Promotes the Development of Diabetic Retinopathy

BackgroundDiabetic retinopathy (DR) is one of the most common and severe microvascular complications of diabetes. Its a fundus lesion with specific changes, and its specific molecular mechanism is still unclear.\n\nMethodsAll target proteins and markers expression in the study was verified by qPCR and western bloting. The morphology and behavior of human retinal epithelial cells ARPE-19 were analyzed using immunofluorescent and apoptosis detection assays, respectively. And, Small GTPase activity was detected by the GST-pull assay.\n\nResultsWe found that DOCK1 showed high expression in high glucose-induced DR. Moreover, its high expression is positively correlated with Rab31 in tissues. DOCK1 promotes the activation of Rac1 and promotes apoptosis of retinal epithelial cells. Rab31 promotes the degradation of TJ proteins by promoting the transport of TJ proteins from the plasma membrane to the endosomes, thereby affecting the tight junctions of epithelial cells. Inhibition of Rac1 activity can effectively reduce cell apoptosis. Similarly, inhibition of Rab31 activity can significantly inhibit the degradation of TJ proteins.\n\nConclusionThis study based on the high glucose-induced DR cell model reveals the role of two mutually synergistic signaling pathways through the important cytological phenomena of apoptosis and damage of tight junctions. One is the degradation of TJ proteins caused by Rab31-mediated vesicle trafficking, and the other is the apoptosis of retinal epithelial cells mediated by DOCK1-Rac1.

cell biology↗

bioRxiv2017

The fruitENCODE project sheds light on the genetic and epigenetic basis of convergent evolution of climacteric fruit ripening

Fleshy fruit evolved independently multiple times during angiosperm history. Many climacteric fruits utilize the hormone ethylene to regulate ripening. The fruitENCODE project shows there are multiple evolutionary origins of the regulatory circuits that govern climacteric fruit ripening. Eudicot climacteric fruits with recent whole-genome duplications (WGDs) evolved their ripening regulatory systems using the duplicated floral identity genes, while others without WGD utilised carpel senescence genes. The monocot banana uses both leaf senescence and duplicated floral-identity genes, forming two interconnected regulatory circuits. H3K27me3 plays a conserved role in restricting the expression of key ripening regulators and their direct orthologs in both the ancestral dry fruit and non-climacteric fleshy fruit species. Our findings suggest that evolution of climacteric ripening was constrained by limited availability of signalling molecules and genetic and epigenetic materials, and WGD provided new resources for plants to circumvent this limit. Understanding these different ripening mechanisms makes it possible to design tailor-made ripening traits to improve quality, yield and minimize postharvest losses.\n\nOne Sentence SummaryThe fruitENCODE project discovered three evolutionary origins of the regulatory circuits that govern climacteric fruit ripening.

genomics↗