EMBO J . . . The Rofudu team revealed the dense distribution of Neurexins mediated calcium channels in the pre-synaptic activity area.

The construction of neural circuits in the brain depends on the establishment of specific and complex chemical synapses between neurons to perform dynamic information processing.highly ordered presynaptic and postsynaptic structures and their precise riveting are essential for normal synaptic formation and function, especially for rapid and accurate information transmission.in addition, synapses are not a single linear information transmission unit, and their diversity and plasticity are necessary for specific neuronal circuits to perform neural computation.therefore, understanding how specific neurons form precise synaptic connections and how specific synapses achieve different physiological characteristics is the key to ultimately understanding brain information processing.neurexins, as a highly conserved presynaptic cell adhesion molecule, is closely related to various neuropsychiatric diseases.in vertebrates, neurexins are encoded by three different genes (nrxn1, nrxn2 and nrxn3); each gene expresses long α - and short β - neurexin with a separate promoter.in addition, neurexins also has a large number of spliceosomes, resulting in thousands of splicing variants.different subtypes of neurexins and their splice variants present specific expression patterns in different neurons.strong evidence indicates that many subtypes of neurexins and different alternative splicing bodies participate in important and specific functional regulation in the process of synaptic formation and information transmission by interacting with various types of ligands.although a large number of studies have confirmed neurexins as a key presynaptic cell adhesion molecule, the specific role of neurexins in regulating the functional architecture of presynaptic activity area is still lack of systematic research, and how its gene mutation leads to different mental disorders is more elusive.the problems mainly come from two technical challenges.first of all, vertebrate neurexins has three genes, two promoters and many alternative splicing bodies; due to the redundancy of potential functions, it is necessary to completely knock out all neurexins expression in order to systematically study the function of neurexins.secondly, accurate measurement of many parameters that determine the functional characteristics of synapses is very important to analyze the function of neurexins in this synapse; however, this is still impossible in most neuron samples, because most synaptic terminals are very small (usually less than 1 μ m), so it is impossible to effectively carry out patch clamp recording analysis with high resolution.on March 5, 2020, Thomas c s ü dhof of Stanford University School of medicine and Luo Fujun, Guangdong Laboratory of regenerative medicine, published an article in the EMBO journal, revealing the key role of neurexins in presynaptic active zone.in order to overcome the above technical challenges, the researchers used the constructed neurexin1-2-3 triple conditional knockout mice and the cell-specific Cre recombinase (PV CRE mice) to completely knock out all neurexins expression.in addition, in order to systematically analyze the phenotypic changes of synapses caused by knockout of all neurexins, the researchers focused on the classic synaptic model of calyx of held, because the giant nerve terminals of the synapse allow direct and high-resolution analysis of presynaptic calcium channels and transmitter vesicle release characteristics using patch clamp recording technology and membrane capacitance measurement technology.combined with immunohistochemistry and laser confocal microscopy, the researchers found that all neurexins deletions did not affect the formation of calyx of held synapses, but resulted in severe damage to the synaptic function.in order to analyze in detail how neurexins knockout leads to the damage of synaptic function, the researchers used patch clamp technique to record presynaptic calcium current and a variety of calcium regulation methods. The results showed that neurexins knockout did not change the expression of presynaptic calcium channels in presynaptic terminals and their electrophysiological characteristics.however, the absence of neurexins significantly reduced the tight coupling between presynaptic calcium channels and neurotransmitter vesicles, suggesting that the aggregation and distribution of calcium channels in presynaptic active regions may become loose.Br / > in order to further study the gap between the Ca2 + / > channel and the Ca2 + / > Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca2 + / Ca The energy activity was significantly decreased, suggesting that the tight coupling between calcium channel and calcium channel was damaged.to sum up, the systematic analysis of calyx of held synapses by researchers shows that neurexins specifically mediates the tight distribution of calcium channels in presynaptic active regions, thus playing a key role in regulating the precision and intensity of synaptic transmission.LUO Fujun research group of Guangdong Provincial Laboratory of regenerative medicine recruited Luo Fujun research group of Guangdong Provincial Laboratory of regenerative medicine. The research group focused on the synaptic and molecular mechanisms of neural circuits, and systematically analyzed the neural circuits by using transgenic mice and molecular and genetic means, combined with patch clamp recording, optical imaging, immunohistochemistry and behavioral science and other interdisciplinary technologies How to establish and regulate synaptic connections specifically to mediate animal behavior.Professor Thomas s ü dhof from Stanford University (2013 Nobel Prize winner in physiology and medicine), and his main work has been published in top academic journals such as neuron, EMBA J, PNAs, cell reports, J neuroscience as the first author / corresponding author. Associate Researcher (co PI) 1. Graduated from well-known universities or research institutes at home and abroad, and obtained a doctor's degree in Mathematics / Biology / medicine and other related majors; 2. Published research papers in important journals in this field as the first author; 3 They are good at listening, speaking, reading and writing in Chinese and English and have the ability to carry out research independently; 4. They have good teamwork spirit, strong sense of responsibility, and can actively assist and guide other laboratory personnel; 5. They have more than two years of postdoctoral experience or excellent doctoral graduates, aged no more than 40 years; postdoctoral 1 He graduated from a well-known university or Research Institute at home and abroad with a doctor's degree in mathematics, biology, medicine and other related majors; 2. He has published research papers in international academic journals, showing good academic development potential and love neuroscience; 3. He has good English reading and writing skills; 4 5. Within three years after graduation, the doctor should be no more than 35 years old and in good health.Assistant Researcher 1. Graduated from universities or research institutes at home and abroad, with master's degree or above in Mathematics / Biology / medicine, or more than two years of research work experience; 2. Good English reading and writing skills; 3. Rigorous study style, love of scientific research, hard work, sense of responsibility and team spirit; 1 He graduated from universities at home and abroad, and obtained bachelor's degree or above in Mathematics / Biology / medicine and other related majors; 2. Strong communication and expression ability and organization and coordination ability; 3. Good writing ability in Chinese and English; 4 He is mainly responsible for the administrative affairs of the research group and the daily operation of the laboratory, including the ordering of common reagents and consumables; the examination and reimbursement of laboratory expenses; the management of various laboratory documents; the reception of meetings, ticketing and the traffic arrangement of relevant researchers; 5. The work is conscientious and responsible, with cheerful personality and enthusiasm.remuneration: 1. Provide internationally competitive salary (annual salary system, 360000 + associate researcher, 320000 postdoctoral researcher, 180000 assistant researcher, 120000 scientific research assistant); 2. Provide sufficient scientific research funds and conditions; give corresponding subsidies and Performance Awards according to work ability and performance; 3 Support postdoctoral to apply for all kinds of national and Guangdong Provincial talent projects during their stay in the station, such as "Pearl River talent plan" of Guangdong Province, National Natural Science Foundation of China and China Postdoctoral Science Fund, etc.; 4. Pay five insurances and one fund and collective account of Guangzhou City; 5. Refer to relevant regulations of Provincial Laboratory of regenerative medicine for other welfare benefits.application methods: 1. For interested applicants, please send their resumes, the names and contact information of the three referees (telephone / email), copies of academic certificate, electronic version of published articles, and personal research experience, interests and career goals (except for scientific research assistant who should be employed) to: Luo_ fujun@grmh-gdl.cn 2. We promise to keep all the materials submitted by the employer strictly confidential and evaluate the candidates' resume, research results, research plan and development potential; 3. If the candidates meet the requirements in the preliminary examination, the specific time, place and relevant matters of the interview will be informed by e-mail; 4 Candidates who fail to meet the requirements of the preliminary examination will not be notified any more. If they do not receive an email within three months, it will be deemed as failing the preliminary examination by default; the original link: for recruitment information, please click the link: recruitment summary of the research group in the first half of 2020 (0101-0307) 2020-03-08; the second half of 2019: recruitment summary of research group (0701-1231) 2020-01-26