The Lysosomal Membrane Protein LAMP2A Promotes Autophagic Flux and Prevents SNCA-induced Parkinson Disease-like Symptoms in the Drosophila Brain

Overview

Journal Autophagy

Specialty Cell Biology

Date 2018 Jul 11

PMID 29989488

Citations 55

Authors

Abdul-Raouf Issa

Jun Sun

Celine Petitgas

Ana Mesquita

Amina Dulac

Marion Robin

Bertrand Mollereau

Andreas Jenny

Baya Cherif-Zahar

Serge Birman

Affiliations

Soon will be listed here.

Abstract

Abbreviations: Act5C: actin 5C; a.E.: after eclosion; Atg5: autophagy-related 5; Atg8a/LC3: autophagy-related 8a; CMA: chaperone-mediated autophagy; DHE: dihydroethidium; elav: embryonic lethal abnormal vision; eMI: endosomal microautophagy; ESCRT: endosomal sorting complexes required for transport; GABARAP: GABA typeA receptor-associated protein; Hsc70-4: heat shock protein cognate 4; HSPA8/Hsc70: heat shock protein family A (Hsp70) member 8; LAMP2: lysosomal associated membrane protein 2; MDA: malondialdehyde; PA-mCherry: photoactivable mCherry; PBS: phosphate-buffered saline; PCR: polymerase chain reaction; PD: Parkinson disease; Ref(2)P/p62: refractory to sigma P; ROS: reactive oxygen species; RpL32/rp49: ribosomal protein L32; RT-PCR: reverse transcription polymerase chain reaction; SING: startle-induced negative geotaxis; SNCA/α-synuclein: synuclein alpha; SQSTM1/p62: sequestosome 1; TBS: Tris-buffered saline; UAS: upstream activating sequence.

Citing Articles

Risk Assessment of RNAi-Based Potential Pesticide ds and Its Homologues for and Non-Target Organisms.

Li K, Chen T, Li Y, Sun K, Pang K, Yu X Insects. 2025; 16(2).

PMID: 40003854 PMC: 11855984. DOI: 10.3390/insects16020225.

Chaperone-Mediated Autophagy Reactivation Protects Against Severe Acute Pancreatitis-Associated Liver Injury Through Upregulating Keap1/Nrf2 Signaling Pathway and Inhibiting NLRP3 Inflammasome Activation.

Li Z, Du M, Wang J, Zhao X, Qu Y, Zhang D Cell Biochem Biophys. 2025; .

PMID: 39998716 DOI: 10.1007/s12013-025-01677-7.

A novel lncRNA FAM151B-DT regulates autophagy and degradation of aggregation prone proteins.

Renganathan A, Minaya M, Broder M, Alfradique-Dunham I, Moritz M, Bhagat R medRxiv. 2025; .

PMID: 39974060 PMC: 11838976. DOI: 10.1101/2025.01.22.25320997.

The role of programmed cell death in organ dysfunction induced by opportunistic pathogens.

Wang Y, Weng L, Wu X, Du B Crit Care. 2025; 29(1):43.

PMID: 39856779 PMC: 11761187. DOI: 10.1186/s13054-025-05278-x.

Parkinson's disease models and death signaling: what do we know until now?.

Pedrao L, Medeiros P, Leandro E, Falquetto B Front Neuroanat. 2024; 18:1419108.

PMID: 39533977 PMC: 11555652. DOI: 10.3389/fnana.2024.1419108.

References

Vanhooren V, Navarrete Santos A, Voutetakis K, Petropoulos I, Libert C, Simm A . Protein modification and maintenance systems as biomarkers of ageing. Mech Ageing Dev. 2015; 151:71-84. DOI: 10.1016/j.mad.2015.03.009. View

Scott R, Schuldiner O, Neufeld T . Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev Cell. 2004; 7(2):167-78. DOI: 10.1016/j.devcel.2004.07.009. View

Cuervo A, Stefanis L, Fredenburg R, Lansbury P, Sulzer D . Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science. 2004; 305(5688):1292-5. DOI: 10.1126/science.1101738. View

Eskelinen E, Illert A, Tanaka Y, Schwarzmann G, Blanz J, von Figura K . Role of LAMP-2 in lysosome biogenesis and autophagy. Mol Biol Cell. 2002; 13(9):3355-68. PMC: 124165. DOI: 10.1091/mbc.e02-02-0114. View

Demontis F, Perrimon N . FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell. 2010; 143(5):813-25. PMC: 3066043. DOI: 10.1016/j.cell.2010.10.007. View

Mukherjee A, Patel B, Koga H, Cuervo A, Jenny A . Selective endosomal microautophagy is starvation-inducible in Drosophila. Autophagy. 2016; 12(11):1984-1999. PMC: 5103356. DOI: 10.1080/15548627.2016.1208887. View

Huttenhower C, Haley E, Hibbs M, Dumeaux V, Barrett D, Coller H . Exploring the human genome with functional maps. Genome Res. 2009; 19(6):1093-106. PMC: 2694471. DOI: 10.1101/gr.082214.108. View

Ktistakis N, Tooze S . Digesting the Expanding Mechanisms of Autophagy. Trends Cell Biol. 2016; 26(8):624-635. DOI: 10.1016/j.tcb.2016.03.006. View

Morell C, Bort A, Vara-Ciruelos D, Ramos-Torres A, Altamirano-Dimas M, Diaz-Laviada I . Up-Regulated Expression of LAMP2 and Autophagy Activity during Neuroendocrine Differentiation of Prostate Cancer LNCaP Cells. PLoS One. 2016; 11(9):e0162977. PMC: 5023108. DOI: 10.1371/journal.pone.0162977. View

10.

Cuervo A, Dice J . Regulation of lamp2a levels in the lysosomal membrane. Traffic. 2001; 1(7):570-83. DOI: 10.1034/j.1600-0854.2000.010707.x. View

11.

DeVorkin L, Gorski S . Monitoring autophagic flux using Ref(2)P, the Drosophila p62 ortholog. Cold Spring Harb Protoc. 2014; 2014(9):959-66. DOI: 10.1101/pdb.prot080333. View

12.

Huynh K, Eskelinen E, Scott C, Malevanets A, Saftig P, Grinstein S . LAMP proteins are required for fusion of lysosomes with phagosomes. EMBO J. 2007; 26(2):313-24. PMC: 1783450. DOI: 10.1038/sj.emboj.7601511. View

13.

Rothaug M, Stroobants S, Schweizer M, Peters J, Zunke F, Allerding M . LAMP-2 deficiency leads to hippocampal dysfunction but normal clearance of neuronal substrates of chaperone-mediated autophagy in a mouse model for Danon disease. Acta Neuropathol Commun. 2015; 3:6. PMC: 4359523. DOI: 10.1186/s40478-014-0182-y. View

14.

Kiffin R, Christian C, Knecht E, Cuervo A . Activation of chaperone-mediated autophagy during oxidative stress. Mol Biol Cell. 2004; 15(11):4829-40. PMC: 524731. DOI: 10.1091/mbc.e04-06-0477. View

15.

Botella J, Bayersdorfer F, Schneuwly S . Superoxide dismutase overexpression protects dopaminergic neurons in a Drosophila model of Parkinson's disease. Neurobiol Dis. 2008; 30(1):65-73. DOI: 10.1016/j.nbd.2007.11.013. View

16.

Jang Y, Perez V, Song W, Lustgarten M, Salmon A, Mele J . Overexpression of Mn superoxide dismutase does not increase life span in mice. J Gerontol A Biol Sci Med Sci. 2009; 64(11):1114-25. PMC: 2759571. DOI: 10.1093/gerona/glp100. View

17.

Xilouri M, Stefanis L . Chaperone mediated autophagy in aging: Starve to prosper. Ageing Res Rev. 2016; 32:13-21. DOI: 10.1016/j.arr.2016.07.001. View

18.

Xu J, Kao S, Lee F, Song W, Jin L, Yankner B . Dopamine-dependent neurotoxicity of alpha-synuclein: a mechanism for selective neurodegeneration in Parkinson disease. Nat Med. 2002; 8(6):600-6. DOI: 10.1038/nm0602-600. View

19.

Xu T, Kumar S, Denton D . Characterization of Autophagic Responses in Drosophila melanogaster. Methods Enzymol. 2017; 588:445-465. DOI: 10.1016/bs.mie.2016.09.089. View

20.

Komatsu M, Waguri S, Koike M, Sou Y, Ueno T, Hara T . Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell. 2007; 131(6):1149-63. DOI: 10.1016/j.cell.2007.10.035. View