LYST deficiency impairs autophagic lysosome reformation in neurons and alters lysosome number and size.
Autolysosome tubule
Autolysosomes
Chediak–Higashi syndrome
Lysosome fission
Protolysosomes
iPSC
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
28 Jan 2023
28 Jan 2023
Historique:
received:
22
07
2022
accepted:
08
01
2023
revised:
11
12
2022
entrez:
27
1
2023
pubmed:
28
1
2023
medline:
1
2
2023
Statut:
epublish
Résumé
Chediak-Higashi syndrome (CHS) is a rare, autosomal recessive disorder caused by biallelic mutations in the lysosomal trafficking regulator (LYST) gene. Even though enlarged lysosomes and/or lysosome-related organelles (LROs) are the typical cellular hallmarks of CHS, they have not been investigated in human neuronal models. Moreover, how and why the loss of LYST function causes a lysosome phenotype in cells has not been elucidated. We report that the LYST-deficient human neuronal model exhibits lysosome depletion accompanied by hyperelongated tubules extruding from enlarged autolysosomes. These results have also been recapitulated in neurons differentiated from CHS patients' induced pluripotent stem cells (iPSCs), validating our model system. We propose that LYST ensures the correct fission/scission of the autolysosome tubules during autophagic lysosome reformation (ALR), a crucial process to restore the number of free lysosomes after autophagy. We further demonstrate that LYST is recruited to the lysosome membrane, likely to facilitate the fission of autolysosome tubules. Together, our results highlight the key role of LYST in maintaining lysosomal homeostasis following autophagy and suggest that ALR dysregulation is likely associated with the neurodegenerative CHS phenotype.
Identifiants
pubmed: 36707427
doi: 10.1007/s00018-023-04695-x
pii: 10.1007/s00018-023-04695-x
doi:
Substances chimiques
Vesicular Transport Proteins
0
LYST protein, human
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
53Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.
Références
Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, Peng J, Mi N, Zhao Y, Liu Z, Wan F, Hailey DW et al (2010) Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465:942–946. https://doi.org/10.1038/nature09076
doi: 10.1038/nature09076
pubmed: 20526321
pmcid: 2920749
Ferguson SM (2018) Axonal transport and maturation of lysosomes. Curr Opin Neurobiol 51:45–51. https://doi.org/10.1016/j.conb.2018.02.020
doi: 10.1016/j.conb.2018.02.020
pubmed: 29529416
pmcid: 6066426
Lie PPY, Nixon RA (2019) Lysosome trafficking and signaling in health and neurodegenerative diseases. Neurobiol Dis 122:94–105. https://doi.org/10.1016/j.nbd.2018.05.015
doi: 10.1016/j.nbd.2018.05.015
pubmed: 29859318
Winckler B, Faundez V, Maday S, Cai Q, Guimas Almeida C, Zhang H (2018) The endolysosomal system and proteostasis: from development to degeneration. J Neurosci 38:9364–9374. https://doi.org/10.1523/JNEUROSCI.1665-18.2018
doi: 10.1523/JNEUROSCI.1665-18.2018
pubmed: 30381428
pmcid: 6209849
Sharma P, Nicoli E-R, Serra-Vinardell J, Morimoto M, Toro C, Malicdan MCV, Introne WJ (2019) Chediak-Higashi syndrome: a review of the past, present, and future. Drug Discov Today Dis Models 31:31–36
doi: 10.1016/j.ddmod.2019.10.008
pubmed: 33424983
pmcid: 7793027
Kaplan J, De Domenico I, Ward DM (2008) Chediak-Higashi syndrome. Curr Opin Hematol 15:22–29. https://doi.org/10.1097/MOH.0b013e3282f2bcce
doi: 10.1097/MOH.0b013e3282f2bcce
pubmed: 18043242
Introne W, Boissy RE, Gahl WA (1999) Clinical, molecular, and cell biological aspects of Chediak-Higashi syndrome. Mol Genet Metab 68:283–303. https://doi.org/10.1006/mgme.1999.2927
doi: 10.1006/mgme.1999.2927
pubmed: 10527680
Barbosa MD, Nguyen QA, Tchernev VT, Ashley JA, Detter JC, Blaydes SM, Brandt SJ, Chotai D, Hodgman C, Solari RC, Lovett M et al (1996) Identification of the homologous beige and Chediak-Higashi syndrome genes. Nature 382:262–265. https://doi.org/10.1038/382262a0
doi: 10.1038/382262a0
pubmed: 8717042
pmcid: 2893578
Nagle DL, Karim MA, Woolf EA, Holmgren L, Bork P, Misumi DJ, McGrail SH, Dussault BJ Jr, Perou CM, Boissy RE, Duyk GM et al (1996) Identification and mutation analysis of the complete gene for Chediak-Higashi syndrome. Nat Genet 14:307–311. https://doi.org/10.1038/ng1196-307
doi: 10.1038/ng1196-307
pubmed: 8896560
Kypri E, Schmauch C, Maniak M, De Lozanne A (2007) The BEACH protein LvsB is localized on lysosomes and postlysosomes and limits their fusion with early endosomes. Traffic (Copenhagen, Denmark) 8:774–783. https://doi.org/10.1111/j.1600-0854.2007.00567.x
doi: 10.1111/j.1600-0854.2007.00567.x
pubmed: 17488289
Perou CM, Leslie JD, Green W, Li L, Ward DM, Kaplan J (1997) The Beige/Chediak-Higashi syndrome gene encodes a widely expressed cytosolic protein. J Biol Chem 272:29790–29794. https://doi.org/10.1074/jbc.272.47.29790
doi: 10.1074/jbc.272.47.29790
pubmed: 9368050
Durchfort N, Verhoef S, Vaughn MB, Shrestha R, Adam D, Kaplan J, Ward DM (2012) The enlarged lysosomes in beige j cells result from decreased lysosome fission and not increased lysosome fusion. Traffic 13:108–119. https://doi.org/10.1111/j.1600-0854.2011.01300.x
doi: 10.1111/j.1600-0854.2011.01300.x
pubmed: 21985295
Sepulveda FE, Burgess A, Heiligenstein X, Goudin N, Menager MM, Romao M, Cote M, Mahlaoui N, Fischer A, Raposo G, Menasche G et al (2015) LYST controls the biogenesis of the endosomal compartment required for secretory lysosome function. Traffic 16:191–203. https://doi.org/10.1111/tra.12244
doi: 10.1111/tra.12244
pubmed: 25425525
Rudelius M, Osanger A, Kohlmann S, Augustin M, Piontek G, Heinzmann U, Jennen G, Russ A, Matiasek K, Stumm G, Schlegel J (2006) A missense mutation in the WD40 domain of murine Lyst is linked to severe progressive Purkinje cell degeneration. Acta Neuropathol 112:267–276. https://doi.org/10.1007/s00401-006-0092-6
doi: 10.1007/s00401-006-0092-6
pubmed: 16791600
Hedberg-Buenz A, Dutca LM, Larson DR, Meyer KJ, Soukup DA, van der Heide CJ, Mercer HE, Wang K, Anderson MG (2019) Mouse models and strain-dependency of Chediak-Higashi syndrome-associated neurologic dysfunction. Sci Rep 9:6752. https://doi.org/10.1038/s41598-019-42159-0
doi: 10.1038/s41598-019-42159-0
pubmed: 31043676
pmcid: 6494809
Trantow CM, Hedberg-Buenz A, Iwashita S, Moore SA, Anderson MG (2010) Elevated oxidative membrane damage associated with genetic modifiers of Lyst-mutant phenotypes. PLoS Genet. 6:e1001008. https://doi.org/10.1371/journal.pgen.1001008
doi: 10.1371/journal.pgen.1001008
pubmed: 20617205
pmcid: 2895641
Wang C, Ward ME, Chen R, Liu K, Tracy TE, Chen X, Xie M, Sohn PD, Ludwig C, Meyer-Franke A, Karch CM et al (2017) Scalable production of iPSC-derived human neurons to identify tau-lowering compounds by high-content screening. Stem Cell Rep 9:1221–1233. https://doi.org/10.1016/j.stemcr.2017.08.019
doi: 10.1016/j.stemcr.2017.08.019
Fernandopulle MS, Prestil R, Grunseich C, Wang C, Gan L, Ward ME (2018) Transcription factor-mediated differentiation of human iPSCs into neurons. Curr Protoc Cell Biol. 79:e51. https://doi.org/10.1002/cpcb.51
doi: 10.1002/cpcb.51
pubmed: 29924488
pmcid: 6993937
Perou CM, Kaplan J (1993) Chediak-Higashi syndrome is not due to a defect in microtubule-based lysosomal mobility. J Cell Sci 106(Pt 1):99–107. https://doi.org/10.1242/jcs.106.1.99
doi: 10.1242/jcs.106.1.99
pubmed: 8270647
Wang C, Telpoukhovskaia MA, Bahr BA, Chen X, Gan L (2018) Endo-lysosomal dysfunction: a converging mechanism in neurodegenerative diseases. Curr Opin Neurobiol 48:52–58. https://doi.org/10.1016/j.conb.2017.09.005
doi: 10.1016/j.conb.2017.09.005
pubmed: 29028540
Son JH, Shim JH, Kim KH, Ha JY, Han JY (2012) Neuronal autophagy and neurodegenerative diseases. Exp Mol Med 44:89–98. https://doi.org/10.3858/emm.2012.44.2.031
doi: 10.3858/emm.2012.44.2.031
pubmed: 22257884
pmcid: 3296817
Yap CC, Digilio L, McMahon LP, Garcia ADR, Winckler B (2018) Degradation of dendritic cargos requires Rab7-dependent transport to somatic lysosomes. J Cell Biol 217:3141–159. https://doi.org/10.1083/jcb.201711039
doi: 10.1083/jcb.201711039
pubmed: 29907658
pmcid: 6122995
Cheng XT, Xie YX, Zhou B, Huang N, Farfel-Becker T, Sheng ZH (2018) Characterization of LAMP1-labeled nondegradative lysosomal and endocytic compartments in neurons. J Cell Biol 217:3127–3139. https://doi.org/10.1083/jcb.201711083
doi: 10.1083/jcb.201711083
pubmed: 29695488
pmcid: 6123004
Gil-Krzewska A, Saeed MB, Oszmiana A, Fischer ER, Lagrue K, Gahl WA, Introne WJ, Coligan JE, Davis DM, Krzewski K (2017) An actin cytoskeletal barrier inhibits lytic granule release from natural killer cells in patients with Chediak-Higashi syndrome. J Allergy Clin Immunol 142:914–27.e6. https://doi.org/10.1016/j.jaci.2017.10.040
doi: 10.1016/j.jaci.2017.10.040
pubmed: 29241728
Holland P, Torgersen ML, Sandvig K, Simonsen A (2014) LYST affects lysosome size and quantity, but not trafficking or degradation through autophagy or endocytosis. Traffic 15:1390–1405. https://doi.org/10.1111/tra.12227
doi: 10.1111/tra.12227
pubmed: 25216107
Burkhardt JK, Wiebel FA, Hester S, Argon Y (1993) The giant organelles in beige and Chediak-Higashi fibroblasts are derived from late endosomes and mature lysosomes. J Exp Med 178:1845–1856. https://doi.org/10.1084/jem.178.6.1845
doi: 10.1084/jem.178.6.1845
pubmed: 7902407
Lee JH, Yu WH, Kumar A, Lee S, Mohan PS, Peterhoff CM, Wolfe DM, Martinez-Vicente M, Massey AC, Sovak G, Uchiyama Y et al (2010) Lysosomal proteolysis and autophagy require presenilin 1 and are disrupted by Alzheimer-related PS1 mutations. Cell 141:1146–1158. https://doi.org/10.1016/j.cell.2010.05.008
doi: 10.1016/j.cell.2010.05.008
pubmed: 20541250
pmcid: 3647462
Chen CS, Chen WN, Zhou M, Arttamangkul S, Haugland RP (2000) Probing the cathepsin D using a BODIPY FL-pepstatin A: applications in fluorescence polarization and microscopy. J Biochem Biophys Methods 42:137–151. https://doi.org/10.1016/s0165-022x(00)00048-8
doi: 10.1016/s0165-022x(00)00048-8
pubmed: 10737220
Serra-Vinardell J, Sandler MB, Pak E, Zheng W, Dutra A, Introne W, Gahl WA, Christine Malicdan M (2020) Generation and characterization of four Chediak-Higashi Syndrome (CHS) induced pluripotent stem cell (iPSC) lines. Stem Cell Res. https://doi.org/10.1016/j.scr.2020.101883
doi: 10.1016/j.scr.2020.101883
pubmed: 32619719
Zhang Y, Pak C, Han Y, Ahlenius H, Zhang Z, Chanda S, Marro S, Patzke C, Acuna C, Covy J, Xu W et al (2013) Rapid single-step induction of functional neurons from human pluripotent stem cells. Neuron 78:785–798. https://doi.org/10.1016/j.neuron.2013.05.029
doi: 10.1016/j.neuron.2013.05.029
pubmed: 23764284
pmcid: 3751803
Li MA, Turner DJ, Ning Z, Yusa K, Liang Q, Eckert S, Rad L, Fitzgerald TW, Craig NL, Bradley A (2011) Mobilization of giant piggyBac transposons in the mouse genome. Nucleic Acids Res. 39:e148. https://doi.org/10.1093/nar/gkr764
doi: 10.1093/nar/gkr764
pubmed: 21948799
pmcid: 3239208
Park MA, Jung HS, Slukvin I (2018) Genetic engineering of human pluripotent stem cells using PiggyBac transposon system. Curr Protoc Stem Cell Biol. 47:e63. https://doi.org/10.1002/cpsc.63
doi: 10.1002/cpsc.63
pubmed: 30281932
Woodard LE, Wilson MH (2015) PiggyBac-Ing models and new therapeutic strategies. Trends Biotechnol 33:525–533. https://doi.org/10.1016/j.tibtech.2015.06.009
doi: 10.1016/j.tibtech.2015.06.009
pubmed: 26211958
pmcid: 4663986
Boland B, Kumar A, Lee S, Platt FM, Wegiel J, Yu WH, Nixon RA (2008) Autophagy induction and autophagosome clearance in neurons: relationship to autophagic pathology in Alzheimer’s disease. J Neurosci 28:6926–6937. https://doi.org/10.1523/jneurosci.0800-08.2008
doi: 10.1523/jneurosci.0800-08.2008
pubmed: 18596167
pmcid: 2676733
Min Y, Xu W, Liu D, Shen H, Xu Y, Zhang S, Zhang L, Wang H (2013) Earle’s balanced salts solution and rapamycin differentially regulate the Bacillus Calmette-Guerin-induced maturation of human dendritic cells. Acta Biochim Biophys Sin (Shanghai) 45:162–169. https://doi.org/10.1093/abbs/gms117
doi: 10.1093/abbs/gms117
pubmed: 23302514
Palmisano I, Della Chiara G, D’Ambrosio RL, Huichalaf C, Brambilla P, Corbetta S, Riba M, Piccirillo R, Valente S, Casari G, Mai A et al (2012) Amino acid starvation induces reactivation of silenced transgenes and latent HIV-1 provirus via down-regulation of histone deacetylase 4 (HDAC4). Proc Natl Acad Sci U S A 109:E2284–E2293. https://doi.org/10.1073/pnas.1202174109
doi: 10.1073/pnas.1202174109
pubmed: 22826225
pmcid: 3427085
Munson MJ, Allen GF, Toth R, Campbell DG, Lucocq JM, Ganley IG (2015) mTOR activates the VPS34-UVRAG complex to regulate autolysosomal tubulation and cell survival. EMBO J 34:2272–2290. https://doi.org/10.15252/embj.201590992
doi: 10.15252/embj.201590992
pubmed: 26139536
pmcid: 4585463
Lattao R, Rangone H, Llamazares S, Glover DM (2021) Mauve/LYST limits fusion of lysosome-related organelles and promotes centrosomal recruitment of microtubule nucleating proteins. Dev Cell 56:1000-1013.e6. https://doi.org/10.1016/j.devcel.2021.02.019
doi: 10.1016/j.devcel.2021.02.019
pubmed: 33725482
pmcid: 8024676
Hung V, Udeshi ND, Lam SS, Loh KH, Cox KJ, Pedram K, Carr SA, Ting AY (2016) Spatially resolved proteomic mapping in living cells with the engineered peroxidase APEX2. Nat Protoc 11:456–475. https://doi.org/10.1038/nprot.2016.018
doi: 10.1038/nprot.2016.018
pubmed: 26866790
pmcid: 4863649
Du W, Su QP, Chen Y, Zhu Y, Jiang D, Rong Y, Zhang S, Zhang Y, Ren H, Zhang C, Wang X et al (2016) Kinesin 1 drives autolysosome tubulation. Dev Cell 37:326–336. https://doi.org/10.1016/j.devcel.2016.04.014
doi: 10.1016/j.devcel.2016.04.014
pubmed: 27219061
Rong Y, McPhee CK, Deng S, Huang L, Chen L, Liu M, Tracy K, Baehrecke EH, Yu L, Lenardo MJ (2011) Spinster is required for autophagic lysosome reformation and mTOR reactivation following starvation. Proc Natl Acad Sci 108:7826–7831. https://doi.org/10.1073/pnas.1013800108
doi: 10.1073/pnas.1013800108
pubmed: 21518918
pmcid: 3093520
Chang J, Lee S, Blackstone C (2014) Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation. J Clin Investig 124:5249–5262. https://doi.org/10.1172/jci77598
doi: 10.1172/jci77598
pubmed: 25365221
pmcid: 4348974
Rong Y, Liu M, Ma L, Du W, Zhang H, Tian Y, Cao Z, Li Y, Ren H, Zhang C, Li L et al (2012) Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation. Nat Cell Biol 14:924–934. https://doi.org/10.1038/ncb2557
doi: 10.1038/ncb2557
pubmed: 22885770
Dai A, Yu L, Wang H-W (2019) WHAMM initiates autolysosome tubulation by promoting actin polymerization on autolysosomes. Nat Commun 10:3699. https://doi.org/10.1038/s41467-019-11694-9
doi: 10.1038/s41467-019-11694-9
pubmed: 31420534
pmcid: 6697732
McGrath MJ, Eramo MJ, Gurung R, Sriratana A, Gehrig SM, Lynch GS, Lourdes SR, Koentgen F, Feeney SJ, Lazarou M, McLean CA et al (2021) Defective lysosome reformation during autophagy causes skeletal muscle disease. J Clin Investig. https://doi.org/10.1172/jci135124
doi: 10.1172/jci135124
pubmed: 33119550
pmcid: 7773396
Schulze RJ, Weller SG, Schroeder B, Krueger EW, Chi S, Casey CA, McNiven MA (2013) Lipid droplet breakdown requires dynamin 2 for vesiculation of autolysosomal tubules in hepatocytes. J Cell Biol 203:315–326. https://doi.org/10.1083/jcb.201306140
doi: 10.1083/jcb.201306140
pubmed: 24145164
pmcid: 3812963
Maday S, Holzbaur EL (2016) Compartment-specific regulation of autophagy in primary neurons. J Neurosci 36:5933–5945. https://doi.org/10.1523/jneurosci.4401-15.2016
doi: 10.1523/jneurosci.4401-15.2016
pubmed: 27251616
pmcid: 4887563
Mizushima N, Yamamoto A, Matsui M, Yoshimori T, Ohsumi Y (2004) In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 15:1101–1111. https://doi.org/10.1091/mbc.e03-09-0704
doi: 10.1091/mbc.e03-09-0704
pubmed: 14699058
pmcid: 363084
Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147:728–741. https://doi.org/10.1016/j.cell.2011.10.026
doi: 10.1016/j.cell.2011.10.026
pubmed: 22078875
Varga RE, Khundadze M, Damme M, Nietzsche S, Hoffmann B, Stauber T, Koch N, Hennings JC, Franzka P, Huebner AK, Kessels MM et al (2015) In vivo evidence for lysosome depletion and impaired autophagic clearance in hereditary spastic paraplegia type SPG11. PLoS Genet 11:e1005454. https://doi.org/10.1371/journal.pgen.1005454
doi: 10.1371/journal.pgen.1005454
pubmed: 26284655
pmcid: 4540459
Boutry M, Branchu J, Lustremant C, Pujol C, Pernelle J, Matusiak R, Seyer A, Poirel M, Chu-Van E, Pierga A, Dobrenis K et al (2018) Inhibition of lysosome membrane recycling causes accumulation of gangliosides that contribute to neurodegeneration. Cell Rep 23:3813–3826. https://doi.org/10.1016/j.celrep.2018.05.098
doi: 10.1016/j.celrep.2018.05.098
pubmed: 29949766
Khundadze M, Ribaudo F, Hussain A, Stahlberg H, Brocke-Ahmadinejad N, Franzka P, Varga R-E, Zarkovic M, Pungsrinont T, Kokal M, Ganley IG et al (2021) Mouse models for hereditary spastic paraplegia uncover a role of PI4K2A in autophagic lysosome reformation. Autophagy 17:3690–3706. https://doi.org/10.1080/15548627.2021.1891848
doi: 10.1080/15548627.2021.1891848
pubmed: 33618608
pmcid: 8632344
Dehay B, Bové J, Rodríguez-Muela N, Perier C, Recasens A, Boya P, Vila M (2010) Pathogenic lysosomal depletion in Parkinson’s disease. J Neurosci 30:12535–12544. https://doi.org/10.1523/jneurosci.1920-10.2010
doi: 10.1523/jneurosci.1920-10.2010
pubmed: 20844148
pmcid: 6633458
Magalhaes J, Gegg ME, Migdalska-Richards A, Doherty MK, Whitfield PD, Schapira AHV (2016) Autophagic lysosome reformation dysfunction in glucocerebrosidase deficient cells: relevance to Parkinson disease. Hum Mol Genet 25:3432–3445. https://doi.org/10.1093/hmg/ddw185
doi: 10.1093/hmg/ddw185
pubmed: 27378698
pmcid: 5179940
Komatsu M, Waguri S, Chiba T, Murata S, Iwata J-i, Tanida I, Ueno T, Koike M, Uchiyama Y, Kominami E, Tanaka K (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441:880–884. https://doi.org/10.1038/nature04723
doi: 10.1038/nature04723
pubmed: 16625205
Marks MS, Heijnen HF, Raposo G (2013) Lysosome-related organelles: unusual compartments become mainstream. Curr Opin Cell Biol 25:495–505. https://doi.org/10.1016/j.ceb.2013.04.008
doi: 10.1016/j.ceb.2013.04.008
pubmed: 23726022
pmcid: 3729921
Ripoll L, Heiligenstein X, Hurbain I, Domingues L, Figon F, Petersen KJ, Dennis MK, Houdusse A, Marks MS, Raposo G, Delevoye C (2018) Myosin VI and branched actin filaments mediate membrane constriction and fission of melanosomal tubule carriers. J Cell Biol 217:2709–2726. https://doi.org/10.1083/jcb.201709055
doi: 10.1083/jcb.201709055
pubmed: 29875258
pmcid: 6080934