China Education Equipment Purchasing Network News: The Journal of Biological Chemistry published the latest research results of the research team of Song Baoliang from the Institute of Biochemistry and Cell Research, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences on the regulation of small GTPase Cdc42 to regulate the transport of NPC1L1 protein to plasma membrane The study found that low cholesterol signal stimulates the activation of Cdc42, and the active Cdc42 can bind to NPC1L1 protein. At the same time, active Cdc42 mediates the dynamic assembly of branched microfilaments through the sequential activation of downstream effectors N-WASP and Arp2 / 3 complex, promotes the dissociation of NPC1L1 protein from Rab11a, and promotes MyoVb to transport NPC1L1 to the plasma membrane. The Cdc42 liver-specific knockout mouse model further proved that the tissue localization and cholesterol absorption function of NPC1L1 depend on Cdc42.
This work was mainly completed by Xie Chang, a PhD student. The project was funded by the Ministry of Science and Technology, the National Natural Science Foundation of China, the Chinese Academy of Sciences and the Shanghai Municipal Science and Technology Commission.
The so-called cardio-cerebrovascular disease is a collective term for diseases of the heart and blood vessels. With the improvement of living standards and the change of life rhythm, the “three high diseases†(that is, hypertension, hyperglycemia and hyperlipidemia) called “rich diseasesâ€, and the use of antihypertensive drugs by elderly people with hypertension are exquisite and principled As for the choice of antihypertensive drugs for the elderly, the prevalence of hypertension gradually increases with age. 40% to 45% of the elderly over 60 years old suffer from hypertension and also suffer from high blood sugar or high blood fat.
Another important cause of cardiovascular and cerebrovascular diseases is caused by abnormal metabolism of smooth muscle cells in blood vessel walls. It is well known that blood vessel tissue completes the metabolic process in a certain period like other tissues of the human body, but because the new cell tissue cannot be formed normally, the blood vessel wall itself has a "defect", which is easy to produce inflammation. Vascular contraction is not smooth, just like An old and dilapidated pipeline may block or break at any time. The blood vessel is an important channel for blood circulation. At the same time, he is also dominated by the nervous system, so abnormal nervous system can also lead to blood supply disorders. Therefore, the causes of cardiovascular and cerebrovascular diseases are multi-faceted. Do not simply consider the impact of blood changes on blood vessels. You must consider them comprehensively, carefully analyze the causes of cardiovascular and cerebrovascular diseases, and carry out multiple treatments. Effective and fundamental.
Excessive intake of cholesterol in the diet is one of the causes of cardiovascular and cerebrovascular diseases. Niemann-Pick Type C1-Like 1 (NPC1L1) protein is a key protein that mediates the absorption of dietary cholesterol in the small intestine. When the cell cholesterol level is low, the NPC1L1 protein will be transported to the plasma membrane. Supplying cholesterol to the cell will cause the NPC1L1 protein and cholesterol to be swallowed into the cell together. Previous work revealed that NPC1L1 protein transport depends on microfilament and MyoVb · Rab11a · Rab11-FIP2 ternary complex, but how cholesterol regulates this process is unclear.
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