Emerging roles for human glycolipid transfer protein superfamily members in the regulation of autophagy, inflammation, and cell death. (April 2020)

• Record Type: Journal Article
• Authors: Mishra, Shrawan K.; Gao, Yong-Guang; Zou, Xianqiong; Stephenson, Daniel J.; Malinina, Lucy; Hinchcliffe, Edward H.; Chalfant, Charles E.; Brown, Rhoderick E.
• Is Part Of: Progress in lipid research. Volume 78(2020)
• Publication Date: 2020-04
• Subjects: Glycolipid transfer protein superfamily -- Sphingolipid homeostasis -- Autophagy -- Inflammasomes -- Necroptosis -- Eicosanoids -- Cytokines -- Sphingolipid rheostat -- Phosphoglyceride regulatory binding; accelerated cell death-11 ACD11 -- acyl-coenzyme A binding domain containing 3 ACBD3 -- age-related macular degeneration AMD -- autophagy-related protein 5 ATG5 -- autophagy-related protein 9A ATG9A -- ceramide Cer -- ceramide-1-phosphate transfer protein CPTP -- ceramide transfer protein CERT -- C-reactive protein CRP -- endoplasmic reticulum ER -- galactosylceramide GalCer -- globotriaosylceramide Gb3 -- glucosylceramide GlcCer -- glycolipid transfer protein GLTP -- glycolipid transfer protein domain-containing protein-2 GLTPD2 -- glycolipid transfer protein homology GLTPH -- glycosphingolipids GSLs -- hepatitis C virus HCV -- human epidermal growth factor receptor 2 HER2 -- interleukin-1β IL-1β -- interleukin-18 IL-18 -- lactosylceramide LacCer -- lipid transfer proteins LTPs -- LTPs anchored at membrane contact sites LAMs -- mammalian-target-of-rapamycin mTOR -- mixed lineage kinase domain-like MLKL -- disialosyllactosylceramide GD3 -- monosialosyldihexosylganglioside GM3 -- monosialosyltetrahexosylganglioside GM1 -- microtubule-associated protein 1A/1B-light chain 3 LC3 -- LC3-conjugated to phosphadiylethanolamine LC3-II -- NLR family pyrin domain containing 3 NLRP3 -- NLR family caspase recruitment domain CARD -- containing 4 NLRC4 -- 1-palmitoyl-2-oleoyl phosphatidylcholine POPC -- 1-palmitoyl-2-oleoyl phosphatidylglycerol POPG -- 1-palmitoyl-2-oleoyl phosphatidylserine POPS -- IVA phospholipase A2 cPLA2α -- phosphatidylinositol 4-phosphate PI-4P -- phosphatidylinositol 4-phosphate adaptor protein-2 FAPP2 -- pleckstrin homology PH -- programmed cell death PCD -- rapid-amplification-of-cDNA-ends (RACE)-PCR -- Ras-related Rab33b-guanosine triphosphatase–activating protein GAP -- receptor-interacting protein kinase 3 RIPK-3 -- regulator of G-protein signaling 3 RGP3 -- ribosomal protein S6 kinase p70S6K -- soluble Fas ligand FasL -- sequestosome 1 SQSTM1 or p62 -- RNAi-induced CPTP depletion CPTPi -- specificity protein 1/specificity protein 3 Sp1/Sp3 -- sphingomyelins SMs -- sphingolipid SL -- sphingosine-1-phosphate S1P -- steroidogenic acute regulatory (Star) protein-related lipid transfer START -- tumor necrosis factor TNF -- tumor necrosis factor-alpha converting enzyme TACE -- unc-51-like kinase 1 ULK1 -- UV-resistance-associated gene UVRAG -- vesicle-associated membrane protein-associated proteins VAMP-associated proteins or VAPs -- WD repeat domain phosphoinositide-interacting protein 1 WIPI-1 or Atg18; Lipids -- Periodicals; Lipids -- Periodicals; Lipides -- Périodiques; Lipiden; 572.57
• DOI: 10.1016/j.plipres.2020.101031
• Languages: English
• ISSNs: 0163-7827

Abstract

Abstract: Glycolipid transfer proteins (GLTPs) were first identified over three decades ago as ~24kDa, soluble, amphitropic proteins that specifically accelerate the intermembrane transfer of glycolipids. Upon discovery that GLTPs use a unique, all-α-helical, two-layer 'sandwich' architecture (GLTP-fold) to bind glycosphingolipids (GSLs), a new protein superfamily was born. Structure/function studies have provided exquisite insights defining features responsible for lipid headgroup selectivity and hydrophobic 'pocket' adaptability for accommodating hydrocarbon chains of differing length and unsaturation. In humans, evolutionarily-modified GLTP-folds have been identified with altered sphingolipid specificity, e. g. ceramide-1-phosphate transfer protein (CPTP), phosphatidylinositol 4-phosphate adaptor protein-2 (FAPP2) which harbors a GLTP-domain and GLTPD2. Despite the wealth of structural data (>40 Protein Data Bank deposits), insights into the in vivo functional roles of GLTP superfamily members have emerged slowly. In this review, recent advances are presented and discussed implicating human GLTP superfamily members as important regulators of: i ) pro-inflammatory eicosanoid production associated with Group-IV cytoplasmic phospholipase A2 ; ii ) autophagy and inflammasome assembly that drive surveillance cell release of interleukin-1β and interleukin-18 inflammatory cytokines; iii ) cell cycle arrest and necroptosis induction in certain colon cancer cell lines. The effects exerted by GLTP superfamily members appear linked to their ability to regulate sphingolipid homeostasis by acting in either transporter and/or sensor capacities. These timely findings are opening new avenues for future cross-disciplinary, translational medical research involving GLTP-fold proteins in human health and disease. Such avenues include targeted regulation of specific GLTP superfamily members to alter sphingolipid levels as a therapeutic means for combating viral infection, neurodegenerative conditions and circumventing chemo-resistance during cancer treatment.