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Multi-omic approach characterises the neuroprotective role of retromer in regulating lysosomal health

Daly, James L., Danson, Chris M., Lewis, Philip A., Zhao, Lu, Riccardo, Sara, Di Filippo, Lucio, Cacchiarelli, Davide, Lee, Daehoon, Cross, Stephen J., Heesom, Kate J., Xiong, Wen-Cheng, Ballabio, Andrea, Edgar, James R., Cullen, Peter J.·2023·Nature Communications
DOI 10.1038/s41467-023-38719-8PMC PMC10227043
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Abstract

Retromer controls cellular homeostasis through regulating integral membrane protein sorting and transport and by controlling maturation of the endo-lysosomal network. Retromer dysfunction, which is linked to neurodegenerative disorders including Parkinson’s and Alzheimer’s diseases, manifests in complex cellular phenotypes, though the precise nature of this dysfunction, and its relation to neurodegeneration, remain unclear. Here, we perform an integrated multi-omics approach to provide precise insight into the impact of Retromer dysfunction on endo-lysosomal health and homeostasis within a human neuroglioma cell model. We quantify widespread changes to the lysosomal proteome, indicative of broad lysosomal dysfunction and inefficient autophagic lysosome reformation, coupled with a reconfigured cell surface proteome and secretome reflective of increased lysosomal exocytosis. Through this global proteomic approach and parallel transcriptomic analysis, we provide a holistic view of Retromer function in regulating lysosomal homeostasis and emphasise its role in neuroprotection.

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  1. Cullen, P. J. & Steinberg, F. To degrade or not to degrade: mechanisms and significance of endocytic recycling. Nat. Rev. Mol. Cell Biol. 19, 679–696 (2018). · DOI · Paper page
  2. Seaman, M. N. J., McCaffery, J. M. & Emr, S. D. A membrane coat complex essential for endosome-to-Golgi retrograde transport in yeast. J. Cell Biol. 142, 665–681 (1998). · DOI · Paper page
  3. Kvainickas, A. et al. Retromer and TBC1D5 maintain late endosomal RAB7 domains to enable amino acid-induced mTORC1 signaling. J. Cell Biol. 218, 3019–3038 (2019). · DOI · Paper page
  4. Jimenez‐Orgaz, A. et al. Control of RAB7 activity and localization through the retromer‐TBC1D5 complex enables RAB7‐dependent mitophagy. EMBO J. 37, 235–254 (2017). · DOI · Paper page
  5. Seaman, M. N. J. J., Harbour, M. E., Tattersall, D., Read, E. & Bright, N. Membrane recruitment of the cargo-selective retromer subcomplex is catalysed by the small GTPase Rab7 and inhibited by the Rab-GAP TBC1D5. J. Cell Sci. 122, 2371–2382 (2009). · DOI · Paper page
  6. Carosi, J. M. et al. Retromer regulates the lysosomal clearance of MAPT/tau. Autophagy 00, 1–21 (2020).
  7. Bi, F., Li, F., Huang, C. & Zhou, H. Pathogenic mutation in VPS35 impairs its protection against MPP(+) cytotoxicity. Int. J. Biol. Sci. 9, 149–155 (2013). · DOI
  8. Sullivan, C. P. et al. Retromer disruption promotes amyloidogenic APP processing. Neurobiol. Dis. 43, 338–345 (2011). · DOI
  9. Simoes, S. et al. Tau and other proteins found in Alzheimer’s disease spinal fluid are linked to retromer-mediated endosomal traffic in mice and humans. Sci. Transl. Med. 12, eaba6334 (2020). · DOI · Paper page
  10. Small, S. A. et al. Model-guided microarray implicates the retromer complex in Alzheimer’s disease. Ann. Neurol. 58, 909–919 (2005). · DOI · Paper page
  11. Zimprich, A. et al. A mutation in VPS35, encoding a subunit of the retromer complex, causes late-onset Parkinson disease. Am. J. Hum. Genet. 89, 168–175 (2011). · DOI · Paper page
  12. Vilariño-Güell, C. et al. VPS35 mutations in parkinson disease. Am. J. Hum. Genet. 89, 162–167 (2011). · DOI · Paper page
  13. Rovelet-Lecrux, A. et al. De novo deleterious genetic variations target a biological network centered on Aβ peptide in early-onset Alzheimer disease. Mol. Psychiatry 20, 1046–1056 (2015). · DOI · Paper page
  14. Sargent, D. et al. Neuronal VPS35 deletion induces spinal cord motor neuron degeneration and early post-natal lethality. Brain Commun. 3, fcab208 (2021). · DOI
  15. Simonetti, B., Danson, C. M., Heesom, K. J. & Cullen, P. J. Sequence-dependent cargo recognition by SNX-BARs mediates retromer-independent transport of CI-MPR. J. Cell Biol. 216, 3695–3712 (2017). · DOI · Paper page
  16. Wang, C. L. et al. VPS35 regulates developing mouse hippocampal neuronal morphogenesis by promoting retrograde trafficking of BACE1. Biol. Open 1, 1248–1257 (2012). · DOI
  17. Tang, F. L. et al. Coupling of terminal differentiation deficit with neurodegenerative pathology in Vps35-deficient pyramidal neurons. Cell Death Differ. 27, 2099–2116 (2020). · DOI · Paper page
  18. Cataldo, A. M. et al. Endocytic pathway abnormalities precede amyloid β deposition in sporadic Alzheimer’s disease and down syndrome: differential effects of APOE genotype and presenilin mutations. Am. J. Pathol. 157, 277–286 (2000). · DOI · Paper page
  19. Crews, L. et al. Selective molecular alterations in the autophagy pathway in patients with Lewy body disease and in models of α-synucleinopathy. PLoS ONE 5, e9313 (2010). · DOI
  20. Shahmoradian, S. H. et al. Lewy pathology in Parkinson’s disease consists of crowded organelles and lipid membranes. Nat. Neurosci. 22, 1099–1109 (2019). · DOI
  21. Abu-Remaileh, M. et al. Lysosomal metabolomics reveals V-ATPase- and mTOR-dependent regulation of amino acid efflux from lysosomes. Science 358, 807–813 (2017). · DOI
  22. Curnock, R., Calcagni, A., Ballabio, A. & Cullen, P. J. TFEB controls retromer expression in response to nutrient availability. J. Cell Biol. 218, 3954–3966 (2019). · DOI · Paper page
  23. Pu, J. et al. BORC, a multisubunit complex that regulates lysosome positioning. Dev. Cell 33, 176–188 (2015). · DOI · Paper page
  24. Bar-Peled, L. & Sabatini, D. M. Regulation of mTORC1 by amino acids. Trends Cell Biol. 24, 400–406 (2014). · DOI · Paper page
  25. Cui, Y. et al. Retromer has a selective function in cargo sorting via endosome transport carriers. J. Cell Biol. 218, 615–631 (2019). · DOI · Paper page
  26. Gegg, M. E. & Schapira, A. H. V. The role of glucocerebrosidase in Parkinson disease pathogenesis. FEBS J. 285, 3591–3603 (2018). · DOI
  27. Gieselmann, V. Lysosomal storage diseases. Biochim. Biophys. Acta—Mol. Basis Dis. 1270, 103–136 (1995). · DOI
  28. Zerial, M. & McBride, H. Rab proteins as membrane organizers. Nat. Rev. Mol. Cell Biol. 2, 107–117 (2001). · DOI · Paper page
  29. Egami, Y. & Araki, N. Rab20 regulates phagosome maturation in RAW264 macrophages during Fc gamma receptor-mediated phagocytosis. PLoS ONE 7, e35663 (2012). · DOI
  30. Jean, S., Cox, S., Nassari, S. & Kiger, A. A. Starvation-induced MTMR13 and RAB21 activity regulates VAMP8 to promote autophagosome–lysosome fusion. EMBO Rep. 16, 297 (2015). · DOI
  31. Kasmapour, B., Gronow, A., Bleck, C. K. E., Hong, W. & Gutierrez, M. G. Size-dependent mechanism of cargo sorting during lysosome-phagosome fusion is controlled by Rab34. Proc. Natl. Acad. Sci. USA 109, 20485–20490 (2012). · DOI
  32. Wilson, G. R. et al. Mutations in RAB39B cause x-linked intellectual disability and early-onset parkinson disease with α-synuclein pathology. Am. J. Hum. Genet. 95, 729–735 (2014). · DOI
  33. Gonçalves, S. A. et al. shRNA-based screen identifies endocytic recycling pathway components that act as genetic modifiers of alpha-synuclein aggregation, secretion and toxicity. PLOS Genet. 12, e1005995 (2016). · DOI
  34. Hashimoto, Y., Shirane, M. & Nakayama, K. I. TMEM55B contributes to lysosomal homeostasis and amino acid–induced mTORC1 activation. Genes Cells 23, 418–434 (2018). · DOI · Paper page
  35. Dai, L. et al. Cholesterol metabolism in neurodegenerative diseases: molecular mechanisms and therapeutic targets. Mol. Neurobiol. 58, 2183–2201 (2021). · DOI
  36. Hu, M. et al. Parkinson’s disease-risk protein TMEM175 is a proton-activated proton channel in lysosomes. Cell 185, 2292–2308.e20 (2022). · DOI · Paper page
  37. O’Brien, R. J. & Wong, P. C. Amyloid precursor protein processing and Alzheimer’s disease. Annu. Rev. Neurosci. 34, 185–204 (2011). · DOI · Paper page
  38. Steinberg, F. et al. A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport. Nat. Cell Biol. 15, 461–471 (2013). · DOI · Paper page
  39. Li, B. et al. The retromer complex safeguards against neural progenitor-derived tumorigenesis by regulating notch receptor trafficking. Elife 7, e38181 (2018). · DOI
  40. Curnock, R. & Cullen, P. J. Mammalian copper homeostasis requires retromer-dependent recycling of the high-affinity copper transporter 1. J. Cell Sci. 133, jcs249201 (2020). · DOI · Paper page
  41. Kvainickas, A. et al. Retromer- and WASH-dependent sorting of nutrient transporters requires a multivalent interaction network with ANKRD50. J. Cell Sci. 130, 382–395 (2017). · DOI
  42. Nakamura, F., Kalb, R. G. & Strittmatter, S. M. Molecular basis of semaphorin-mediated axon guidance. J Neurobiol 44, 219–229 (2000). · DOI
  43. Giniger, E. Notch signaling and neural connectivity. Curr. Opin. Genet. Dev. 22, 339 (2012). · DOI
  44. Ivakine, E. A. et al. Neto2 is a KCC2 interacting protein required for neuronal Cl- regulation in hippocampal neurons. Proc. Natl. Acad. Sci. USA 110, 3561–3566 (2013). · DOI
  45. Vernon, C. G. & Swanson, G. T. Neto2 assembles with kainate receptors in DRG neurons during development and modulates neurite outgrowth in adult sensory neurons. J. Neurosci. 37, 3352 (2017). · DOI
  46. Mahadevan, V. et al. Neto2-null mice have impaired GABAergic inhibition and are susceptible to seizures. Front. Cell. Neurosci. 9, 368 (2015). · DOI
  47. del Puerto, A. et al. Kidins220 deficiency causes ventriculomegaly via SNX27-retromer-dependent AQP4 degradation. Mol. Psychiatry 26, 6411–6426 (2021). · DOI · Paper page
  48. Sebastián-Serrano, Á. et al. Differential regulation of Kidins220 isoforms in Huntington’s disease. Brain Pathol. 30, 120–136 (2020). · DOI
  49. Li, Q. & Südhof, T. C. Cleavage of amyloid-β precursor protein and amyloid-β precursor-like protein by BACE 1. J. Biol. Chem. 279, 10542–10550 (2004). · DOI · Paper page
  50. Matsuda, S. et al. The familial dementia BRI2 gene binds the Alzheimer gene amyloid-β precursor protein and inhibits amyloid-β production. J. Biol. Chem. 280, 28912–28916 (2005). · DOI · Paper page
  51. Medina, D. L. et al. Transcriptional activation of lysosomal exocytosis promotes cellular clearance. Dev. Cell 21, 421–430 (2011). · DOI
  52. Alvarez-Erviti, L. et al. Lysosomal dysfunction increases exosome-mediated alpha-synuclein release and transmission. Neurobiol. Dis. 42, 360–367 (2011). · DOI
  53. Miranda, A. M. et al. Neuronal lysosomal dysfunction releases exosomes harboring APP C-terminal fragments and unique lipid signatures. Nat. Commun. 9, 1–16 (2018). · DOI · Paper page
  54. Ballabio, A. & Bonifacino, J. S. Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat. Rev. Mol. Cell Biol. 21, 101–118 (2020). · DOI · Paper page
  55. Follett, J. et al. The Vps35 D620N mutation linked to Parkinson’s disease disrupts the cargo sorting function of retromer. Traffic 15, 230–244 (2014). · DOI
  56. Bugarcic, A. et al. Vps26A and Vps26B subunits define distinct retromer complexes. Traffic 12, 1759–1773 (2011). · DOI
  57. Rojas, R. et al. Regulation of retromer recruitment to endosomes by sequential action of Rab5 and Rab7. J. Cell Biol. 183, 513–526 (2008). · DOI · Paper page
  58. Hata, S. et al. Alcadein cleavages by amyloid β-precursor protein (APP) α- and γ-secretases generate small peptides, p3-Alcs, indicating Alzheimer disease-related γ-secretase dysfunction. J. Biol. Chem. 284, 36024–36033 (2009). · DOI
  59. Walsh, R. B. et al. Opposing functions for retromer and Rab11 in extracellular vesicle traffic at presynaptic terminals. J. Cell Biol. 220, e202012034 (2021). · DOI
  60. Sardiello, M. et al. A gene network regulating lysosomal biogenesis and function. Science 325, 473–477 (2009). · DOI · Paper page
  61. Settembre, C. et al. A lysosome-to-nucleus signalling mechanism senses and regulates the lysosome via mTOR and TFEB. EMBO J. 31, 1095–1108 (2012). · DOI · Paper page
  62. Palmieri, M. et al. Characterization of the CLEAR network reveals an integrated control of cellular clearance pathways. Hum. Mol. Genet. 20, 3852–3866 (2011). · DOI · Paper page
  63. Peña-Llopis, S. et al. Regulation of TFEB and V-ATPases by mTORC1. EMBO J. 30, 3242–3258 (2011). · DOI
  64. Mansueto, G. et al. Transcription factor EB controls metabolic flexibility during exercise. Cell Metab. 25, 182–196 (2017). · DOI · Paper page
  65. Seaman, M. N. J. Identification of a novel conserved sorting motif required for retromer-mediated endosome-to-TGN retrieval. J. Cell Sci. 120, 2378–2389 (2007). · DOI
  66. Lucas, M. et al. Structural mechanism for cargo recognition by the retromer complex. Cell 167, 1623–1635.e14 (2016). · DOI · Paper page
  67. Ostrowski, M. et al. Rab27a and Rab27b control different steps of the exosome secretion pathway. Nat. Cell Biol. 12, 19–30 (2010). · DOI
  68. Joshi, C. S., Mora, A., Felder, P. A. & Mysorekar, I. U. NRF2 promotes urothelial cell response to bacterial infection by regulating reactive oxygen species and RAB27B expression. Cell Rep. 37, 109856 (2021). · DOI
  69. Underwood, R. et al. The GTPase Rab27b regulates the release, autophagic clearance, and toxicity of alpha-synuclein. J. Biol. Chem. 295, 8005–8016 (2020). · DOI
  70. Underwood, R., Wang, B., Pathak, A., Volpicelli-Daley, L. & Yacoubian, T. A. Rab27 GTPases regulate alpha-synuclein uptake, cell-to-cell transmission, and toxicity. bioRxiv 2020.11.17.387449. https://doi.org/10.1101/2020.11.17.387449 (2020). · DOI
  71. Jia, D. et al. Structural and mechanistic insights into regulation of the retromer coat by TBC1d5. Nat. Commun. 7, 1–11 (2016). · DOI · Paper page
  72. Hesketh, G. et al. VARP is recruited on to endosomes by direct interaction with retromer, where together they function in export to the cell surface. Dev. Cell 29, 591–606 (2014). · DOI · Paper page
  73. Wu, K. et al. BLOC1S1/GCN5L1/BORCS1 is a critical mediator for the initiation of autolysosomal tubulation. Autophagy 17, 3707–3724 (2021). · DOI
  74. McGrath, M. J. et al. Defective lysosome reformation during autophagy causes skeletal muscle disease. J. Clin. Invest. 131, e135124 (2021). · DOI
  75. Mecozzi, V. J. et al. Pharmacological chaperones stabilize retromer to limit APP processing. Nat. Chem. Biol. 10, 443–449 (2014). · DOI · Paper page
  76. Luzio, J. P., Pryor, P. R. & Bright, N. A. Lysosomes: Fusion and function. Nat. Rev. Mol. Cell Biol. 8, 622–632 (2007). · DOI
  77. Chen, Y. & Yu, L. Recent progress in autophagic lysosome reformation. Traffic 18, 358–361 (2017). · DOI
  78. Zavodszky, E. et al. Mutation in VPS35 associated with Parkinson’s disease impairs WASH complex association and inhibits autophagy. Nat. Commun. 5, 3828 (2014). · DOI · Paper page
  79. Pu, J., Keren-Kaplan, T. & Bonifacino, J. S. A Ragulator-BORC interaction controls lysosome positioning in response to amino acid availability. J. Cell Biol. 216, 4183–4197 (2017). · DOI
  80. Yordanov, T. E. et al. Biogenesis of lysosome-related organelles complex-1 (BORC) regulates late endosomal/lysosomal size through PIKfyve-dependent phosphatidylinositol-3,5-bisphosphate. Traffic 20, 674–696 (2019). · DOI
  81. Rong, Y. et al. Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation. Nat. Cell Biol. 14, 924–934 (2012). · DOI · Paper page
  82. Du, W. et al. Kinesin 1 drives autolysosome tubulation. Dev. Cell 37, 326–336 (2016). · DOI
  83. Dai, A., Yu, L. & Wang, H. W. WHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes. Nat. Commun. 10, 3699 (2019). · DOI
  84. Bécot, A., Volgers, C. & van Niel, G. Transmissible endosomal intoxication: a balance between exosomes and lysosomes at the basis of intercellular amyloid propagation. Biomedicines 8, 272 (2020). · DOI
  85. Tang, F. L. et al. VPS35 deficiency or mutation causes dopaminergic neuronal loss by impairing mitochondrial fusion and function. Cell Rep. 12, 1631–1643 (2015). · DOI
  86. Tian, Y. et al. VPS35-deficiency results in an impaired AMPA receptor trafficking and decreased dendritic spine maturation. Mol. Brain 8, 1–12 (2015). · DOI · Paper page
  87. Zhao, L. et al. pHluorin-BACE1-mCherry acts as a reporter for the intracellular distribution of active BACE1 in vitro and in vivo. Cells 8, 474 (2019). · DOI
  88. Costes, S. V. et al. Automatic and quantitative measurement of protein-protein colocalization in live cells. Biophys. J. 86, 3993–4003 (2004). · DOI
  89. Brenes, A., Hukelmann, J., Bensaddek, D. & Lamond, A. I. Multibatch TMT reveals false positives, batch effects and missing values. Mol. Cell. Proteomics 18, 1967–1980 (2019). · DOI · Paper page
  90. Xiong, Y. et al. A comparison of mRNA sequencing with random primed and 3′-directed libraries. Sci. Reports 7, 1–12 (2017).
  91. Dobin, A. et al. STAR: ultrafast universal RNA-seq aligner. Bioinformatics 29, 15–21 (2013). · DOI · Paper page
  92. Anders, S., Pyl, P. T. & Huber, W. HTSeq—a Python framework to work with high-throughput sequencing data. Bioinformatics 31, 166–169 (2015). · DOI · Paper page
  93. Robinson, M. D., McCarthy, D. J. & Smyth, G. K. edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 26, 139–140 (2010). · DOI · Paper page
  94. Mootha, V. K. et al. PGC-1α-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat. Genet. 34, 267–273 (2003). · DOI · Paper page
  95. Durinck, S., Spellman, P. T., Birney, E. & Huber, W. Mapping identifiers for the integration of genomic datasets with the R/Bioconductor package biomaRt. Nat. Protoc. 4, 1184–1191 (2009). · DOI
  96. Goedhart, J. & Luijsterburg, M. S. VolcaNoseR is a web app for creating, exploring, labeling and sharing volcano plots. Sci. Rep. 10, 1–5 (2020). · DOI
  97. Zhou, Y. et al. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun. 10, 1–10 (2019). · DOI · Paper page
  98. Mi, H. et al. Protocol Update for large-scale genome and gene function analysis with the PANTHER classification system (v.14.0). Nat. Protoc. 14, 703–721 (2019). · DOI
  99. Perez-Riverol, Y. et al. The PRIDE database resources in 2022: a hub for mass spectrometry-based proteomics evidences. Nucleic Acids Res. 50, D543–D552 (2022). · DOI · Paper page
  100. Edgar, R., Domrachev, M. & Lash, A. E. Gene expression omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207–210 (2002). · DOI · Paper page

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Metadata

Authors
Daly, J. L., Danson, C. M., Lewis, P. A., Zhao, L., Riccardo, S., Di Filippo, L., Cacchiarelli, D., Lee, D., Cross, S. J., Heesom, K. J., Xiong, W.-C., Ballabio, A., Edgar, J. R., & Cullen, P. J.
Venue
Nature Communications
Publisher
Springer Science and Business Media LLC
Published
2023-05-29
Volume
14
Issue
1
ISSN
2041-1723
DOI
10.1038/s41467-023-38719-8
PMC
PMC10227043
Cited by
45
References
14
Language
en
Licence
Funders
  • Wellcome Trust (104568/Z/14/Z, 220260/Z/20/Z, 203959/Z/16/Z, 225128/Z/22/Z)
  • RCUK | Medical Research Council (MR/L007363/1, MR/P018807/1)
  • Royal Society (RSRP/R1/211004)

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