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This Week in PNAS: Jun 4, 2019

Researchers from the UK and Poland found that engineering phototropins in the model organism Arabidopsis thaliana led to an increase in light sensitivity, as they report in the Proceedings of the National Academy of Sciences this week. Using target mutagenesis in vitro, they altered the photocycle lifetime of the phototropins phot1 and phot2, which are activated by blue light and are involved in photosynthetic efficiency. Plants then engineered to have slower cycling phototropins exhibited increased biomass production in low-light conditions. This suggested to the researchers that protein engineering approached could be applied to increase plant photosynthetic capacity and growth.

Also in PNAS this week, a team of Chinese researchers reports that UBE3A, in which maternally inherited mutations lead to Angelman syndrome, ubiquitinates PTPA. By stable-isotope labeling amino acids, the researchers found PTPA is a substrate upon which UBE3A acts. In mice, maternal loss of Ube3a led to increased PTPA levels and PP2A activity, while a maternal 15q11-13 duplication downregulated both PTPA and PP2A activity. Using the small molecule LB-100, the researchers could inhibit PP2A activity in the Angelman syndrome mouse model, which led to improved phenotypes.

Stanford University researchers found that young blood harbors two factors — THBS4 and SPARCL1 — that contribute to its ability to improve cognitive ability in mice. They report that serum taken from young mice, but not serum taken from old mice could synaptic connectivity when applied to neurons transdifferentiated from human embryonic stem cells. Based on a mass spectrometry analysis, they found that THBS4 and SPARCL1 were enriched in the serum of young mice, and, in culture, noted that they increased dendritic arborization. Additionally, SPARCL1 increased the NMDA receptor-mediated synaptic responses. This led the researchers to suggest THBS4 and SPARCL1 could be rejuvenation factors that increase synaptic connectivity by improving dendritic arborization as well as synaptic formation and transmission.