Abstract
The discovery that apolipoprotein L1 (APOL1) is the trypanolytic factor of human serum raised interest about the function of APOLs, especially following the unexpected finding that in addition to their protective action against sleeping sickness, APOL1 C‐terminal variants also cause kidney disease. Based on the analysis of the structure and trypanolytic activity of APOL1, it was proposed that APOLs could function as ion channels of intracellular membranes and be involved in mechanisms triggering programmed cell death. In this review, the recent finding that APOL1 and APOL3 inversely control the synthesis of phosphatidylinositol‐4‐phosphate (PI(4)P) by the Golgi PI(4)‐kinase IIIB (PI4KB) is commented. APOL3 promotes Ca2+‐dependent activation of PI4KB, but due to their increased interaction with APOL3, APOL1 C‐terminal variants can inactivate APOL3, leading to reduction of Golgi PI(4)P synthesis. The impact of APOLs on several pathological processes that depend on Golgi PI(4)P levels is discussed. I propose that through their effect on PI4KB activity, APOLs control not only actomyosin activities related to vesicular trafficking, but also the generation and elongation of autophagosomes induced by inflammation.
Highlights
Since the identification of apolipoprotein L1 (APOL1) as component of serum high-density lipoprotein particles [1], the nature of the functions performed by the members of the human apolipoprotein L (APOL) family remained elusive
The aim of this review was to discuss the implications of this finding in terms of diseases influenced by PI(4)P levels
We found that APOL3 binds with high affinity to calneuron 1 (CALN-1), a PI(4)-kinase IIIB (PI4KB) inhibitor [40], but only at low Ca2+ concentrations, under opposite Ca2+ conditions as compared to neuronal calcium sensor 1 (NCS-1)
Summary
Since the identification of APOL1 as component of serum high-density lipoprotein particles [1], the nature of the functions performed by the members of the human apolipoprotein L (APOL) family remained elusive. A role linked to viral infection was suggested for APOL1 and APOL3, given the strong induction of their expression through the viral inflammatory TLR3/TRIF pathway [5,6], and the linkage of G1- or G2-induced kidney disease with HIV infection [7]. In both dendritic cells and kidney podocytes, APOL1 and APOL3 were found to be involved in apoptosis triggered by the viral mimetic agent poly(I:C) [6,8], and in macrophages, APOL1 was reported to restrict HIV-1 infection [9].
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