JNK相互作用蛋白3(JIP3)蛋白最初被认为是一种调节丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)信号通路的支架蛋白,近年来陆续被发现在神经元的胞内运输、神经元轴突的发育以及大脑发育过程中起到重要作用。通过对国...JNK相互作用蛋白3(JIP3)蛋白最初被认为是一种调节丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)信号通路的支架蛋白,近年来陆续被发现在神经元的胞内运输、神经元轴突的发育以及大脑发育过程中起到重要作用。通过对国内外文献的研究与分析,本文对JIP3蛋白分子结构及其生理功能等方面进行较全面的综述,为进一步深入的功能研究和应用提供有价值的参考。展开更多
Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties.However,the interplay between endosomal phosphoinositides metabolism and innate immunity...Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties.However,the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood.Here,our findings highlight the evolutionary continuity of RAB-10/Rab10’s involvement in regulating innate immunity.Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa,an increase in RAB-10 activity was observed in the intestine.Conversely,when RAB-10 was absent,the intestinal diacylglycerols(DAGs)decreased,and the animal’s response to the pathogen was impaired.Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector,facilitating the recruitment of phospholipase EGL-8 to endosomes.This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate(PI(4,5)P2)and an elevation of DAGs,as well as the activation of the PMK-1/p38 MAPK innate immune pathway.It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP)and the recruitment of EGL-8.Moreover,we ascertained that the rise in RAB-10 activity,due to infection,was attributed to the augmented expression of LET-413/Erbin,and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase.Hence,this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.展开更多
文摘JNK相互作用蛋白3(JIP3)蛋白最初被认为是一种调节丝裂原活化蛋白激酶(mitogen-activated protein kinases,MAPK)信号通路的支架蛋白,近年来陆续被发现在神经元的胞内运输、神经元轴突的发育以及大脑发育过程中起到重要作用。通过对国内外文献的研究与分析,本文对JIP3蛋白分子结构及其生理功能等方面进行较全面的综述,为进一步深入的功能研究和应用提供有价值的参考。
基金The National Key R&D Program of China(2021YFA1300302)the National Natural Science Foundation of China(32320103007,32130027)+1 种基金the National Science Fund for Distinguished Young Scholars(31825017)the Major Research Plan of the Natural Science Foundation of China(92154001)to A.Shi.
文摘Endosomes are characterized by the presence of various phosphoinositides that are essential for defining the membrane properties.However,the interplay between endosomal phosphoinositides metabolism and innate immunity is yet to be fully understood.Here,our findings highlight the evolutionary continuity of RAB-10/Rab10’s involvement in regulating innate immunity.Upon infection of Caenorhabditis elegans with Pseudomonas aeruginosa,an increase in RAB-10 activity was observed in the intestine.Conversely,when RAB-10 was absent,the intestinal diacylglycerols(DAGs)decreased,and the animal’s response to the pathogen was impaired.Further research revealed that UNC-16/JIP3 acts as an RAB-10 effector,facilitating the recruitment of phospholipase EGL-8 to endosomes.This leads to a decrease in endosomal phosphatidylinositol 4,5-bisphosphate(PI(4,5)P2)and an elevation of DAGs,as well as the activation of the PMK-1/p38 MAPK innate immune pathway.It is noteworthy that the dimerization of UNC-16 is a prerequisite for its interaction with RAB-10(GTP)and the recruitment of EGL-8.Moreover,we ascertained that the rise in RAB-10 activity,due to infection,was attributed to the augmented expression of LET-413/Erbin,and the nuclear receptor NHR-25/NR5A1/2 was determined to be indispensable for this increase.Hence,this study illuminates the significance of endosomal PI(4,5)P2 catabolism in boosting innate immunity and outlines an NHR-25-mediated mechanism for pathogen detection in intestinal epithelia.
