PDF(Pubmed)
Abstract：
The functions of human Apolipoproteins L (APOLs) are poorly understood, but involve diverse activities like lysis of bloodstream trypanosomes and intracellular bacteria, modulation of viral infection and induction of apoptosis, autophagy, and chronic kidney disease. Based on recent work, I propose that the basic function of APOLs is the control of membrane dynamics, at least in the Golgi and mitochondrion. Together with neuronal calcium sensor-1 (NCS1) and calneuron-1 (CALN1), APOL3 controls the activity of phosphatidylinositol-4-kinase-IIIB (PI4KB), involved in both Golgi and mitochondrion membrane fission. Whereas secreted APOL1 induces African trypanosome lysis through membrane permeabilization of the parasite mitochondrion, intracellular APOL1 conditions non-muscular myosin-2A (NM2A)-mediated transfer of PI4KB and APOL3 from the Golgi to the mitochondrion under conditions interfering with PI4KB-APOL3 interaction, such as APOL1 C-terminal variant expression or virus-induced inflammatory signalling. APOL3 controls mitophagy through complementary interactions with the membrane fission factor PI4KB and the membrane fusion factor vesicle-associated membrane protein-8 (VAMP8). In mice, the basic APOL1 and APOL3 activities could be exerted by mAPOL9 and mAPOL8, respectively. Perspectives regarding the mechanism and treatment of APOL1-related kidney disease are discussed, as well as speculations on additional APOLs functions, such as APOL6 involvement in adipocyte membrane dynamics through interaction with myosin-10 (MYH10).
摘要：
人类载脂蛋白L（APOL）的功能知之甚少，但涉及多种活动，如血液锥虫和细胞内细菌的裂解，调节病毒感染和诱导细胞凋亡，自噬,和慢性肾病。根据最近的工作，我认为APOL的基本功能是控制膜动力学，至少在高尔基体和线粒体.连同神经元钙传感器-1（NCS1）和钙神经元-1（CALN1），APOL3控制磷脂酰肌醇-4-激酶-IIIB（PI4KB）的活性，参与高尔基体和线粒体膜裂变。分泌的APOL1通过寄生虫线粒体的膜透化诱导非洲锥虫裂解，在干扰PI4KB-APOL3相互作用的条件下，细胞内APOL1调节非肌肉肌球蛋白2A（NM2A）介导的PI4KB和APOL3从高尔基体转移到线粒体，例如APOL1C端变体表达或病毒诱导的炎症信号传导。APOL3通过与膜裂变因子PI4KB和膜融合因子囊泡相关膜蛋白8(VAMP8)的互补相互作用来控制有丝分裂。在老鼠身上,基本的APOL1和APOL3活性可以分别由mAPOL9和mAPOL8发挥。关于APOL1相关肾脏疾病的机制和治疗的观点进行了讨论，以及对其他APOL功能的猜测，例如APOL6通过与肌球蛋白10（MYH10）相互作用参与脂肪细胞膜动力学。
