Biology subjects

Sharon, R.

Publications and source records attributed to Sharon, R..

3 recordsLinked to original sources

bioRxiv2025

α-Synuclein Activates the PI3K/AKT Pathway to Drive Lipid Droplets Accumulation: Implications for Parkinson's Disease

Growing evidence supports a metabolic component in Parkinsons disease (PD). - Synuclein (-Syn), a protein central to the onset and progression of PD, facilitates the accumulation of neuronal lipid droplets, which are implicated in disease pathology. We report that AKT is hyper-phosphorylated in PD brains and show that -Syn enhances p110 activity by facilitating palmitoylated Ras localization to the plasma membrane, driving lipid droplet accumulation through PI3K/AKT/mTOR and PPAR{gamma} activation. Phosphorylation of -Syn at Ser129 correlates positively with the localization of Ras to the membrane fraction and with accumulation of lipid droplets. In-vivo treatment of young, asymptomatic -SynA53T transgenic mice with GDC-0084 (paxalisib), a blood- brain barrier-permeable PI3K inhibitor, restored healthy AKT activity levels, reduced levels of PSer129 and -Syn oligomers, decreased neuronal lipid droplet accumulation, and promoted lysosomal clustering. These findings establish a role for -Syn in p110 activation during early, asymptomatic stages of the disease and highlight the therapeutic potential of PI3K inhibition as a disease-modifying strategy. Highlight-Syn activates PI3K/AKT by promoting the localization of palmitoylated Ras to membranes, linking metabolic dysfunction to PD.

neuroscience↗

bioRxiv2020

α-Synuclein facilitates endocytosis by elevating the steady-state levels of phosphatidylinositol 4,5-bisphosphate

-Synuclein (-Syn) is a protein implicated in the pathogenesis of Parkinsons disease (PD). It is an intrinsically disordered protein that binds acidic phospholipids. Growing evidence supports a role for -Syn in membrane trafficking, including, mechanisms of endocytosis and exocytosis, although the exact role of -Syn in these mechanisms is currently unclear. Here we have investigated the role of -Syn in membrane trafficking through its association with acidic phosphoinositides (PIPs), such as phosphatidylinositol 4,5-bisphosphate (PI4,5P2) and phosphatidylinositol 3,4-bisphosphate (PI3,4P2). Our results show that -Syn colocalizes with PIP2 and the phosphorylated active form of the clathrin adaptor AP2 at clathrin-coated pits. Using endocytosis of transferrin, an indicator of clathrin mediated endocytosis (CME), we find that -Syn involvement in endocytosis is specifically mediated through PI4,5P2 levels. We further show that the rate of synaptic vesicle (SV) endocytosis is differentially affected by -Syn mutations. In accord with their effects on PI4,5P2 levels at the plasma membrane, the PD associated E46K and A53T mutations further enhance SV endocytosis. However, neither A30P mutation, nor Lysine to Glutamic acid substitutions at the KTKEGV repeat domain of -Syn, that interfere with phospholipid binding, affect SV endocytosis. This study provides evidence for a critical involvement of PIPs in -Syn-mediated membrane trafficking. Significance Statement-Synuclein (-Syn) protein is known for its causative role in Parkinsons disease. -Syn is normally involved in mechanisms of membrane trafficking, including endocytosis, exocytosis and synaptic vesicles cycling. However, a certain degree of controversy regarding the exact role of -Syn in these mechanisms persists. Here we show that -Syn acts to increase plasma membrane levels PI4,5P2 and PI3,4P2 to facilitate clathrin mediated and synaptic vesicles endocytosis. Based on the results, we suggest that -Syn interactions with the acidic phosphoinositides facilitate a shift in their homeostasis to support endocytosis.

neuroscience↗

bioRxiv2018

The sounds of plants - Plants emit remotely-detectable ultrasounds that can reveal plant stress

Stressed plants show altered phenotypes, including changes in color, smell, and shape. Yet, the possibility that plants emit airborne sounds when stressed - similarly to many animals - has not been investigated. Here we show, to our knowledge for the first time, that stressed plants emit airborne sounds that can be recorded remotely, both in acoustic chambers and in greenhouses. We recorded [~]65 dBSPL ultrasonic sounds 10 cm from tomato and tobacco plants, implying that these sounds could be detected by some organisms from up to several meters away. We developed machine learning models that were capable of distinguishing between plant sounds and general noises, and identifying the condition of the plants - dry, cut, or intact - based solely on the emitted sounds. Our results suggest that animals, humans, and possibly even other plants, could use sounds emitted by a plant to gain information about the plants condition. More investigation on plant bioacoustics in general and on sound emission in plants in particular may open new avenues for understanding plants and their interactions with the environment, and it may also have a significant impact on agriculture.

plant biology↗