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Am J Physiol Cell Physiol
2015 Sep 01;3095:C332-47. doi: 10.1152/ajpcell.00142.2015.
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BH3 domain-independent apolipoprotein L1 toxicity rescued by BCL2 prosurvival proteins.
Heneghan JF
,
Vandorpe DH
,
Shmukler BE
,
Giovinazzo JA
,
Giovinnazo JA
,
Raper J
,
Friedman DJ
,
Pollak MR
,
Alper SL
.
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The potent trypanolytic properties of human apolipoprotein L1 (APOL1) can be neutralized by the trypanosome variant surface antigen gene product known as serum resistance-associated protein. However, two common APOL1 haplotypes present uniquely in individuals of West African ancestry each encode APOL1 variants resistant to serum resistance-associated protein, and each confers substantial resistance to human African sleeping sickness. In contrast to the dominantly inherited anti-trypanosomal activity of APOL1, recessive inheritance of these two trypanoprotective APOL1 alleles predisposes to kidney disease. Proposed mechanisms of APOL1 toxicity have included BH3 domain-dependent autophagy and/or ion channel activity. We probed these potential mechanisms by expressing APOL1 in Xenopus laevis oocytes. APOL1 expression in oocytes increased ion permeability and caused profound morphological deterioration (toxicity). Coexpression of BCL2 family members rescued APOL1-associated oocyte toxicity in the order MCL1 ∼ BCLW > BCLXL ∼ BCL2A1 ≫ BCL2. Deletion of nine nominal core BH3 domain residues abolished APOL1-associated toxicity, but missense substitution of the same residues abolished neither oocyte toxicity nor its rescue by coexpressed MCL1. The APOL1 BH3 domain was similarly dispensable for the ability of APOL1 to rescue intact mice from lethal trypanosome challenge. Replacement of most extracellular Na(+) by K(+) also reduced APOL1-associated oocyte toxicity, allowing demonstration of APOL1-associated increases in Ca(2+) and Cl(-) fluxes and oocyte ion currents, which were similarly reduced by MCL1 coexpression. Thus APOL1 toxicity in Xenopus oocytes is BH3-independent, but can nonetheless be rescued by some BCL2 family proteins.
,
Corrigendum.
2015,
Pubmed
Andrews,
Damage control: cellular mechanisms of plasma membrane repair.
2014,
Pubmed
Bhuyan,
Resting membrane potential as a marker of apoptosis: studies on Xenopus oocytes microinjected with cytochrome c.
2001,
Pubmed
,
Xenbase
Bortner,
Cationic gradient reversal and cytoskeleton-independent volume regulatory pathways define an early stage of apoptosis.
2008,
Pubmed
Braun,
Expression of Bcl-x(S) in Xenopus oocytes induces BH3-dependent and caspase-dependent cytochrome c release and apoptosis.
2003,
Pubmed
,
Xenbase
Bunse,
Intracellular cysteine 346 is essentially involved in regulating Panx1 channel activity.
2010,
Pubmed
,
Xenbase
Börjesson,
Intracellular K+ concentration decrease is not obligatory for apoptosis.
2011,
Pubmed
,
Xenbase
Chen,
Differential targeting of prosurvival Bcl-2 proteins by their BH3-only ligands allows complementary apoptotic function.
2005,
Pubmed
Coll,
Neutral sphingomyelinase-induced ceramide triggers germinal vesicle breakdown and oxidant-dependent apoptosis in Xenopus laevis oocytes.
2007,
Pubmed
,
Xenbase
Crawford,
Autophagy hijacked through viroporin-activated calcium/calmodulin-dependent kinase kinase-β signaling is required for rotavirus replication.
2012,
Pubmed
Di Venanzio,
Serratia marcescens ShlA pore-forming toxin is responsible for early induction of autophagy in host cells and is transcriptionally regulated by RcsB.
2014,
Pubmed
Dominguez,
Role of glycogen synthase kinase 3 beta as a negative regulator of dorsoventral axis formation in Xenopus embryos.
1995,
Pubmed
,
Xenbase
Engelhardt,
Effects on channel properties and induction of cell death induced by c-terminal truncations of pannexin1 depend on domain length.
2015,
Pubmed
,
Xenbase
Englund,
A voltage dependent non-inactivating Na+ channel activated during apoptosis in Xenopus oocytes.
2014,
Pubmed
,
Xenbase
Galindo-Moreno,
Apolipoprotein L2 contains a BH3-like domain but it does not behave as a BH3-only protein.
2014,
Pubmed
Genovese,
APOL1 variants and kidney disease in people of recent African ancestry.
2013,
Pubmed
Genovese,
Association of trypanolytic ApoL1 variants with kidney disease in African Americans.
2010,
Pubmed
Gonzalez,
Bacterial pore-forming toxins: the (w)hole story?
2008,
Pubmed
Gonzalez,
Pore-forming toxins induce multiple cellular responses promoting survival.
2011,
Pubmed
Gutsmann,
Molecular mechanisms of interaction of rabbit CAP18 with outer membranes of gram-negative bacteria.
1999,
Pubmed
Gutsmann,
Interaction of CAP18-derived peptides with membranes made from endotoxins or phospholipids.
2001,
Pubmed
Heneghan,
Regulated transport of sulfate and oxalate by SLC26A2/DTDST.
2010,
Pubmed
,
Xenbase
Huang,
An interaction between Bcl-xL and the voltage-dependent anion channel (VDAC) promotes mitochondrial Ca2+ uptake.
2013,
Pubmed
Huang,
Mcl-1 promotes lung cancer cell migration by directly interacting with VDAC to increase mitochondrial Ca2+ uptake and reactive oxygen species generation.
2014,
Pubmed
Johnson,
Features of programmed cell death in intact Xenopus oocytes and early embryos revealed by near-infrared fluorescence and real-time monitoring.
2010,
Pubmed
,
Xenbase
Johnstone,
APOL1 null alleles from a rural village in India do not correlate with glomerulosclerosis.
2012,
Pubmed
Kasembeli,
APOL1 Risk Variants Are Strongly Associated with HIV-Associated Nephropathy in Black South Africans.
2015,
Pubmed
Khatua,
Exon 4-encoded sequence is a major determinant of cytotoxicity of apolipoprotein L1.
2015,
Pubmed
Kloft,
Pro-autophagic signal induction by bacterial pore-forming toxins.
2010,
Pubmed
Kopp,
APOL1 genetic variants in focal segmental glomerulosclerosis and HIV-associated nephropathy.
2011,
Pubmed
Kovacsics,
Transient expression of proteins by hydrodynamic gene delivery in mice.
2014,
Pubmed
Lan,
APOL1 risk variants enhance podocyte necrosis through compromising lysosomal membrane permeability.
2014,
Pubmed
Lecordier,
Identification of Trypanosoma brucei components involved in trypanolysis by normal human serum.
2014,
Pubmed
Liu,
Apolipoprotein l6, a novel proapoptotic Bcl-2 homology 3-only protein, induces mitochondria-mediated apoptosis in cancer cells.
2005,
Pubmed
Liu,
Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia.
2013,
Pubmed
Molina-Portela,
Trypanosome lytic factor, a subclass of high-density lipoprotein, forms cation-selective pores in membranes.
2005,
Pubmed
Molina-Portela,
Distinct roles of apolipoprotein components within the trypanosome lytic factor complex revealed in a novel transgenic mouse model.
2008,
Pubmed
Monajemi,
The apolipoprotein L gene cluster has emerged recently in evolution and is expressed in human vascular tissue.
2002,
Pubmed
Mood,
Contribution of JNK, Mek, Mos and PI-3K signaling to GVBD in Xenopus oocytes.
2004,
Pubmed
,
Xenbase
Muchmore,
X-ray and NMR structure of human Bcl-xL, an inhibitor of programmed cell death.
1996,
Pubmed
Nichols,
Innate immunity pathways regulate the nephropathy gene Apolipoprotein L1.
2015,
Pubmed
Nutt,
Metabolic regulation of oocyte cell death through the CaMKII-mediated phosphorylation of caspase-2.
2005,
Pubmed
,
Xenbase
Park,
Potassium efflux during apoptosis.
2002,
Pubmed
Parys,
The IP3 receptor as a hub for Bcl-2 family proteins in cell death control and beyond.
2014,
Pubmed
Pattingre,
Bcl-2 antiapoptotic proteins inhibit Beclin 1-dependent autophagy.
2005,
Pubmed
Poelvoorde,
Distribution of apolipoprotein L-I and trypanosome lytic activity among primate sera.
2004,
Pubmed
Pérez-Morga,
Apolipoprotein L-I promotes trypanosome lysis by forming pores in lysosomal membranes.
2005,
Pubmed
Sinha,
Molecular basis of the regulation of Beclin 1-dependent autophagy by the gamma-herpesvirus 68 Bcl-2 homolog M11.
2008,
Pubmed
Sinha,
The autophagy effector Beclin 1: a novel BH3-only protein.
2008,
Pubmed
Smith,
The apolipoprotein L family of programmed cell death and immunity genes rapidly evolved in primates at discrete sites of host-pathogen interactions.
2009,
Pubmed
Stephens,
Endosomal localization of the serum resistance-associated protein in African trypanosomes confers human infectivity.
2011,
Pubmed
Sung,
Phosphorylated K-Ras limits cell survival by blocking Bcl-xL sensitization of inositol trisphosphate receptors.
2013,
Pubmed
Tang,
Beauvericin activates Ca2+-activated Cl- currents and induces cell deaths in Xenopus oocytes via influx of extracellular Ca2+.
2005,
Pubmed
,
Xenbase
Thomson,
Human trypanolytic factor APOL1 forms pH-gated cation-selective channels in planar lipid bilayers: relevance to trypanosome lysis.
2015,
Pubmed
Thomson,
Evolution of the primate trypanolytic factor APOL1.
2014,
Pubmed
Tsuchiya,
Anti-apoptotic activity and proteasome-mediated degradation of Xenopus Mcl-1 protein in egg extracts.
2011,
Pubmed
,
Xenbase
Tucker,
Heteromeric channel formation and Ca(2+)-free media reduce the toxic effect of the weaver Kir 3.2 allele.
1996,
Pubmed
,
Xenbase
Tzur,
Missense mutations in the APOL1 gene are highly associated with end stage kidney disease risk previously attributed to the MYH9 gene.
2010,
Pubmed
Vanhamme,
Apolipoprotein L-I is the trypanosome lytic factor of human serum.
2003,
Pubmed
Vanhollebeke,
The function of apolipoproteins L.
2006,
Pubmed
Vanhollebeke,
Human Trypanosoma evansi infection linked to a lack of apolipoprotein L-I.
2006,
Pubmed
Wan,
Apolipoprotein L1, a novel Bcl-2 homology domain 3-only lipid-binding protein, induces autophagic cell death.
2008,
Pubmed
Xong,
A VSG expression site-associated gene confers resistance to human serum in Trypanosoma rhodesiense.
1998,
Pubmed
Youle,
The BCL-2 protein family: opposing activities that mediate cell death.
2008,
Pubmed
Zhaorigetu,
ApoL1, a BH3-only lipid-binding protein, induces autophagic cell death.
2008,
Pubmed