EMBO reports . . . The team found that phosphatase PP2A was involved in regulating the pruning of dendrites during neuronal development.

In the process of animal development, neuronal maturation often requires selective removal of exuberant or unnecessary nerve branches, which is crucial for the establishment of mature neural circuits in animal development.clinical studies have shown that neuronal pruning disorder often exists in some neurological diseases, such as autism and schizophrenia.at present, little is known about the molecular and cellular mechanisms that control neuronal pruning.during the development of Drosophila melanogaster, type IV sensory neurons ddac will prune all dendrite branches and retain the integrity of axons after 16 hours of pupation, and then grow again until the adult stage to form new neural branches and loops.therefore, ddac neurons provide an attractive model for the study of dendrite pruning.Yu Fengwei Laboratory of Singapore Temasek Institute of life sciences has long used the Drosophila model to study the molecular and cellular mechanisms of neuronal pruning, and successively revealed novel ecr-b1 / Sox14 / mica signaling pathway (kirilly, et al., Nature Neuroscience, 2009), epigenetic regulation mechanism (kirilly, et al., neuron, 2011), protein degradation system (Wong, et al, PLoS Biology, 2013; Zhang, et al., developmental cell, 2014; Zong et al., PLoS Biology, 2018), endocytosis (Zhang, et al., development, 2017, 2018), microtubule polarity positive and negative (Wang et al., eLife, 2019) are involved in regulating neuronal pruning.recently, the laboratory published a paper entitled protein phosphate PP2A regulations dentritic microtubule orientation and dendrite pruning in Drosophila in EBO reports, a cooperative Journal of Wiley Association. It was found for the first time that phosphorylase PP2A regulates the polarity of microtubules in Drosophila development, thus affecting the pruning of neurons.this study revealed for the first time that phosphorylase regulates pruning of neurons, which has potential significance for further understanding and treating neurological diseases.in this study, we found that the down-regulated gene microtubule star (MTS) could not completely eliminate ddac neuron dendrites 16 hours after pupation.after analysis, they found that the protein encoded by MTS belongs to the catalytic subunit of phosphorylase PP2A.PP2A of mammals and Drosophila is very conservative in structure and function. It is composed of three different subunits: structural subunit, catalytic subunit and regulatory subunit.next, the researchers found that down-regulation of other subunits, including structural subunits and two regulatory subunits, also caused neuronal pruning disorders.these results confirm for the first time that the phosphorylase PP2A is involved in the regulation of neuronal pruning.the researchers further analyzed the cellular and molecular biological mechanisms of PP2A regulating neuronal pruning, and found that PP2A plays a dual regulatory role in neuronal pruning.first of all, the researchers found that Sox14 / mical signal was significantly down regulated in the PP2A mutant Drosophila, and increasing the level of mical protein could rescue the defect of PP2A mutant neuron pruning.this function is performed by one of the regulatory subunits WDB of PP2A.at the same time, we further found that PP2A controls the microtubule polarity of dendrites through another regulatory subunit TWS. in PP2A mutant, the microtubule polarity of dendrites changed significantly. previous studies, including the eLife article of the same laboratory in 2019, showed that under normal circumstances, the negative pole of most microtubules in dendrites of ddac neurons in Drosophila melanogaster is outward, away from the cell body, and the positive pole is toward the cell body. however, the polarity of microtubules in dendrites changed significantly after PP2A related genes including MTS, pp2a-29b and regulatory subunit TWS were knocked out. the researchers further found that the deletion of PP2A resulted in a significant increase in the protein level of microtubule depolymerization enzyme klp110a, which then changed the polarity of microtubules in dendrites, and finally inhibited dendrite shearing of neurons. in conclusion, the authors found a new participant in neuronal pruning - phosphorylase, and revealed the cellular and molecular biological mechanism of phosphorylase PP2A in regulating neuronal pruning. coincidentally, the team of Dr. Sebastian Rumpf from the University of Minster, Germany, also found that the phosphorylase PP2A regulates dendrite pruning of ddac in Drosophila. They revealed that the phosphorylase PP2A affects the pruning of neurons by regulating microfilaments. the findings of the two research teams further confirmed the important role of phosphorylase PP2A in neuronal pruning, and affected neuronal pruning in different ways. the results of the two studies were published in the latest issue of EMBO reports. it is reported that Professor Yu Fengwei from Temasek Institute of life sciences and National University of Singapore is the corresponding author of the paper. Dr. Rui Menglong and Dr. Kay Siong ng ng are the co first authors of this paper. In addition, Dr. Tang Quan and Dr. Bu Shufeng also participated in the research. Click to read the original text or scan the code to see the details of the original text. Related reading: EMBO reports | Chen Jianguo / Wang Fang team reveals the new mechanism of chronic stress-induced depression; team of Liang Haihua analyzes the regulatory mechanism of biofilm of pathogenic bacteria; EMBO J | Zhu Jiankang / Huang Sanwen team discovered the molecular genetic mechanism of salt tolerance reduction caused by tomato domestication EMBO J | Liu Xingguo / PEI Duanqing team reveals the mystery of IPS reprogramming factor unlocking heterochromatin? Wiley Willie, global leader in research and Education Publishing Academic resources search platform: onlinelibrary.wiley.com