The Function of Apolipoproteins L (APOLs): Relevance for Kidney Disease, Neurotransmission Disorders, Cancer and Viral Infection

Overview

Journal FEBS J

Specialty Biochemistry

Date 2020 Jun 13

PMID 32530132

Citations 14

Authors

Etienne Pays

Affiliations

Soon will be listed here.

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 Ca -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.

Citing Articles

Apolipoprotein-L Functions in Membrane Remodeling.

Pays E Cells. 2025; 13(24.

PMID: 39768205 PMC: 11726835. DOI: 10.3390/cells13242115.

Apolipoprotein-L1 (APOL1): From Sleeping Sickness to Kidney Disease.

Pays E Cells. 2024; 13(20.

PMID: 39451256 PMC: 11506758. DOI: 10.3390/cells13201738.

A natural small molecule alleviates liver fibrosis by targeting apolipoprotein L2.

Gan L, Jiang Q, Huang D, Wu X, Zhu X, Wang L Nat Chem Biol. 2024; 21(1):80-90.

PMID: 39103634 DOI: 10.1038/s41589-024-01704-3.

The Janus-faced functions of Apolipoproteins L in membrane dynamics.

Pays E Cell Mol Life Sci. 2024; 81(1):134.

PMID: 38478101 PMC: 10937811. DOI: 10.1007/s00018-024-05180-9.

Experimental verification and identifying biomarkers related to insomnia.

Wang Q, Liu D, Gao T, Tao Y, Li X, Liu Y Front Neurol. 2023; 14:1189076.

PMID: 38090272 PMC: 10713807. DOI: 10.3389/fneur.2023.1189076.

References

Perez-Morga D, Vanhollebeke B, Paturiaux-Hanocq F, Nolan D, Lins L, Homble F . Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes. Science. 2005; 309(5733):469-72. DOI: 10.1126/science.1114566. View

Piton A, Michaud J, Peng H, Aradhya S, Gauthier J, Mottron L . Mutations in the calcium-related gene IL1RAPL1 are associated with autism. Hum Mol Genet. 2008; 17(24):3965-74. DOI: 10.1093/hmg/ddn300. View

Mirza M, Capozzi L, Xu Y, McCullough L, Liu F . Knockout of vascular early response gene worsens chronic stroke outcomes in neonatal mice. Brain Res Bull. 2013; 98:111-21. PMC: 4275796. DOI: 10.1016/j.brainresbull.2013.07.011. View

Taylor H, Khatua A, Popik W . The innate immune factor apolipoprotein L1 restricts HIV-1 infection. J Virol. 2013; 88(1):592-603. PMC: 3911732. DOI: 10.1128/JVI.02828-13. View

Mimmack M, Ryan M, Baba H, Iritani S, Faull R, McKenna P . Gene expression analysis in schizophrenia: reproducible up-regulation of several members of the apolipoprotein L family located in a high-susceptibility locus for schizophrenia on chromosome 22. Proc Natl Acad Sci U S A. 2002; 99(7):4680-5. PMC: 123707. DOI: 10.1073/pnas.032069099. View

Ng E, Georgiou J, Avila A, Trought K, Mun H, Hodgson M . Mice lacking neuronal calcium sensor-1 show social and cognitive deficits. Behav Brain Res. 2019; 381:112420. DOI: 10.1016/j.bbr.2019.112420. View

Hu C, Klopfer E, Ray P . Human apolipoprotein L1 (ApoL1) in cancer and chronic kidney disease. FEBS Lett. 2012; 586(7):947-55. PMC: 3349435. DOI: 10.1016/j.febslet.2012.03.002. View

Lehrmann E, Colantuoni C, Deep-Soboslay A, Becker K, Lowe R, Huestis M . Transcriptional changes common to human cocaine, cannabis and phencyclidine abuse. PLoS One. 2007; 1:e114. PMC: 1762434. DOI: 10.1371/journal.pone.0000114. View

Genovese G, Friedman D, Ross M, Lecordier L, Uzureau P, Freedman B . Association of trypanolytic ApoL1 variants with kidney disease in African Americans. Science. 2010; 329(5993):841-5. PMC: 2980843. DOI: 10.1126/science.1193032. View

10.

Giannotta M, Fragassi G, Tamburro A, Vanessa C, Luini A, Sallese M . Prohibitin: A Novel Molecular Player in KDEL Receptor Signalling. Biomed Res Int. 2015; 2015:319454. PMC: 4442004. DOI: 10.1155/2015/319454. View

11.

Duchateau P, Pullinger C, Orellana R, Kunitake S, OConnor P, Malloy M . Apolipoprotein L, a new human high density lipoprotein apolipoprotein expressed by the pancreas. Identification, cloning, characterization, and plasma distribution of apolipoprotein L. J Biol Chem. 1997; 272(41):25576-82. DOI: 10.1074/jbc.272.41.25576. View

12.

Apasu J, Schuette D, LaRanger R, Steinle J, Nguyen L, Grosshans H . Neuronal calcium sensor 1 (NCS1) promotes motility and metastatic spread of breast cancer cells in vitro and in vivo. FASEB J. 2018; 33(4):4802-4813. PMC: 6436647. DOI: 10.1096/fj.201802004R. View

13.

Roy M, Tomar D, Singh K, Lakshmi S, Prajapati P, Bhatelia K . TRIM8 regulated autophagy modulates the level of cleaved Caspase-3 subunit to inhibit genotoxic stress induced cell death. Cell Signal. 2018; 48:1-12. DOI: 10.1016/j.cellsig.2018.04.003. View

14.

Karbowski M, Lee Y, Gaume B, Jeong S, Frank S, Nechushtan A . Spatial and temporal association of Bax with mitochondrial fission sites, Drp1, and Mfn2 during apoptosis. J Cell Biol. 2002; 159(6):931-8. PMC: 2173996. DOI: 10.1083/jcb.200209124. View

15.

Schmeisser H, Bekisz J, Zoon K . New function of type I IFN: induction of autophagy. J Interferon Cytokine Res. 2014; 34(2):71-8. PMC: 3924851. DOI: 10.1089/jir.2013.0128. View

16.

Vanhollebeke B, Pays E . The function of apolipoproteins L. Cell Mol Life Sci. 2006; 63(17):1937-44. PMC: 11136045. DOI: 10.1007/s00018-006-6091-x. View

17.

Chu J, Li N, Li F . A risk score staging system based on the expression of seven genes predicts the outcome of bladder cancer. Oncol Lett. 2018; 16(2):2091-2096. PMC: 6036497. DOI: 10.3892/ol.2018.8904. View

18.

Lucken-Ardjomande S, Montessuit S, Martinou J . Contributions to Bax insertion and oligomerization of lipids of the mitochondrial outer membrane. Cell Death Differ. 2008; 15(5):929-37. DOI: 10.1038/cdd.2008.9. View

19.

Johnstone D, Shegokar V, Nihalani D, Rathore Y, Mallik L, Ashish . APOL1 null alleles from a rural village in India do not correlate with glomerulosclerosis. PLoS One. 2013; 7(12):e51546. PMC: 3530541. DOI: 10.1371/journal.pone.0051546. View

20.

Nguyen L, Petri E, Huynh L, Ehrlich B . Characterization of NCS1-InsP3R1 interaction and its functional significance. J Biol Chem. 2019; 294(49):18923-18933. PMC: 6901312. DOI: 10.1074/jbc.RA119.009736. View