Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11

English version České info

Autophagy is a degradative pathway for the removal and subsequent recycling of dysfunctional intracellular components. The material destined for degradation is initially enclosed by a double membrane, the autophagosome. In autolysosomes, which result from fusion of autophagosomes with lysosomes, the material is finally broken down. Recent in vitro data suggested that the protein Spatacsin plays a pivotal role in the regeneration of lysosomes from autolysosomes. Spatacsin is encoded by SPG11, the most common gene mutated in autosomal recessive hereditary spastic paraplegia. Here we show that mice devoid of Spatacsin develop symptoms consistent with spastic paraplegia and progressively loose cortical motoneurons and Purkinje cells. In these mice degenerating neurons have a reduced number of lysosomes available for fusion with autophagosomes and consequently accumulate autolysosome-derived material over time. In the long term this causes death of particularly sensitive neurons like cortical motoneurons and Purkinje cells.

Vyšlo v časopise: Evidence for Lysosome Depletion and Impaired Autophagic Clearance in Hereditary Spastic Paraplegia Type SPG11. PLoS Genet 11(8): e32767. doi:10.1371/journal.pgen.1005454
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005454

Souhrn

Zdroje

1. Fink JK (2014) Hereditary spastic paraplegia: clinical principles and genetic advances. Semin Neurol 34 : 293–305. doi: 10.1055/s-0034-1386767 25192507

2. Novarino G, Fenstermaker AG, Zaki MS, Hofree M, Silhavy JL, et al. (2014) Exome sequencing links corticospinal motor neuron disease to common neurodegenerative disorders. Science 343 : 506–511. doi: 10.1126/science.1247363 24482476

3. Pensato V, Castellotti B, Gellera C, Pareyson D, Ciano C, et al. (2014) Overlapping phenotypes in complex spastic paraplegias SPG11, SPG15, SPG35 and SPG48. Brain 137 : 1907–1920. doi: 10.1093/brain/awu121 24833714

4. Stevanin G, Santorelli FM, Azzedine H, Coutinho P, Chomilier J, et al. (2007) Mutations in SPG11, encoding spatacsin, are a major cause of spastic paraplegia with thin corpus callosum. Nat Genet 39 : 366–372. 17322883

5. Hanein S, Martin E, Boukhris A, Byrne P, Goizet C, et al. (2008) Identification of the SPG15 gene, encoding spastizin, as a frequent cause of complicated autosomal-recessive spastic paraplegia, including Kjellin syndrome. Am J Hum Genet 82 : 992–1002. doi: 10.1016/j.ajhg.2008.03.004 18394578

6. Slabicki M, Theis M, Krastev DB, Samsonov S, Mundwiller E, et al. (2010) A genome-scale DNA repair RNAi screen identifies SPG48 as a novel gene associated with hereditary spastic paraplegia. PLoS Biol 8: e1000408. doi: 10.1371/journal.pbio.1000408 20613862

7. Hirst J, Barlow LD, Francisco GC, Sahlender DA, Seaman MN, et al. (2011) The fifth adaptor protein complex. PLoS Biol 9: e1001170. doi: 10.1371/journal.pbio.1001170 22022230

8. Hirst J, Irving C, Borner GH (2013) Adaptor Protein Complexes AP-4 and AP-5: New Players in Endosomal Trafficking and Progressive Spastic Paraplegia. Traffic 14 : 153–164. doi: 10.1111/tra.12028 23167973

9. Sagona AP, Nezis IP, Pedersen NM, Liestol K, Poulton J, et al. (2010) PtdIns(3)P controls cytokinesis through KIF13A-mediated recruitment of FYVE-CENT to the midbody. Nat Cell Biol 12 : 362–371. doi: 10.1038/ncb2036 20208530

10. Vantaggiato C, Crimella C, Airoldi G, Polishchuk R, Bonato S, et al. (2013) Defective autophagy in spastizin mutated patients with hereditary spastic paraparesis type 15. Brain 136 : 3119–3139. doi: 10.1093/brain/awt227 24030950

11. Perez-Branguli F, Mishra HK, Prots I, Havlicek S, Kohl Z, et al. (2014) Dysfunction of spatacsin leads to axonal pathology in SPG11-linked hereditary spastic paraplegia. Hum Mol Genet 23 : 4859–4874. doi: 10.1093/hmg/ddu200 24794856

12. Hirst J, Borner GH, Edgar J, Hein MY, Mann M, et al. (2013) Interaction between AP-5 and the hereditary spastic paraplegia proteins SPG11 and SPG15. Mol Biol Cell 24 : 2558–2569. doi: 10.1091/mbc.E13-03-0170 23825025

13. Khundadze M, Kollmann K, Koch N, Biskup C, Nietzsche S, et al. (2013) A Hereditary Spastic Paraplegia Mouse Model Supports a Role of ZFYVE26/SPASTIZIN for the Endolysosomal System. PLoS Genet 9: e1003988. doi: 10.1371/journal.pgen.1003988 24367272

14. Renvoise B, Chang J, Singh R, Yonekawa S, FitzGibbon EJ, et al. (2014) Lysosomal abnormalities in hereditary spastic paraplegia types SPG15 and SPG11. Ann Clin Transl Neurol 1 : 379–389. 24999486

15. Chang J, Lee S, Blackstone C (2014) Spastic paraplegia proteins spastizin and spatacsin mediate autophagic lysosome reformation. J Clin Invest 124 : 5249–5262. doi: 10.1172/JCI77598 25365221

16. Shen HM, Mizushima N (2014) At the end of the autophagic road: an emerging understanding of lysosomal functions in autophagy. Trends Biochem Sci 39 : 61–71. doi: 10.1016/j.tibs.2013.12.001 24369758

17. Leone DP, Srinivasan K, Chen B, Alcamo E, McConnell SK (2008) The determination of projection neuron identity in the developing cerebral cortex. Curr Opin Neurobiol 18 : 28–35. doi: 10.1016/j.conb.2008.05.006 18508260

18. Greig LC, Woodworth MB, Galazo MJ, Padmanabhan H, Macklis JD (2013) Molecular logic of neocortical projection neuron specification, development and diversity. Nat Rev Neurosci 14 : 755–769. doi: 10.1038/nrn3586 24105342

19. Martin E, Yanicostas C, Rastetter A, Naini SM, Maouedj A, et al. (2012) Spatacsin and spastizin act in the same pathway required for proper spinal motor neuron axon outgrowth in zebrafish. Neurobiol Dis 48 : 299–308. doi: 10.1016/j.nbd.2012.07.003 22801083

20. Mizushima N, Komatsu M (2011) Autophagy: renovation of cells and tissues. Cell 147 : 728–741. doi: 10.1016/j.cell.2011.10.026 22078875

21. Schule R, Schlipf N, Synofzik M, Klebe S, Klimpe S, et al. (2009) Frequency and phenotype of SPG11 and SPG15 in complicated hereditary spastic paraplegia. J Neurol Neurosurg Psychiatry 80 : 1402–1404. doi: 10.1136/jnnp.2008.167528 19917823

22. Boettger T, Rust MB, Maier H, Seidenbecher T, Schweizer M, et al. (2003) Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold. EMBO J 22 : 5422–5434. 14532115

23. Wahlsten D (1982) Deficiency of corpus callosum varies with strain and supplier of the mice. Brain Res 239 : 329–347. 7093694

24. Beetz C, Koch N, Khundadze M, Zimmer G, Nietzsche S, et al. (2013) A spastic paraplegia mouse model reveals REEP1-dependent ER shaping. J Clin Invest 123 : 4273–4282. doi: 10.1172/JCI65665 24051375

25. Ferreirinha F, Quattrini A, Pirozzi M, Valsecchi V, Dina G, et al. (2004) Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport. J Clin Invest 113 : 231–242. 14722615

26. Tarrade A, Fassier C, Courageot S, Charvin D, Vitte J, et al. (2006) A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition. Hum Mol Genet 15 : 3544–3558. 17101632

27. Pekny M, Nilsson M (2005) Astrocyte activation and reactive gliosis. Glia 50 : 427–434. 15846805

28. Kollmann K, Uusi-Rauva K, Scifo E, Tyynela J, Jalanko A, et al. (2013) Cell biology and function of neuronal ceroid lipofuscinosis-related proteins. Biochim Biophys Acta 1832 : 1866–1881. doi: 10.1016/j.bbadis.2013.01.019 23402926

29. Hehr U, Bauer P, Winner B, Schule R, Olmez A, et al. (2007) Long-term course and mutational spectrum of spatacsin-linked spastic paraplegia. Ann Neurol 62 : 656–665. 18067136

30. Klionsky DJ, Elazar Z, Seglen PO, Rubinsztein DC (2008) Does bafilomycin A1 block the fusion of autophagosomes with lysosomes? Autophagy 4 : 849–850. 18758232

31. Hara T, Nakamura K, Matsui M, Yamamoto A, Nakahara Y, et al. (2006) Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice. Nature 441 : 885–889. 16625204

32. Komatsu M, Waguri S, Chiba T, Murata S, Iwata J, et al. (2006) Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441 : 880–884. 16625205

33. Cao Y, Espinola JA, Fossale E, Massey AC, Cuervo AM, et al. (2006) Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis. J Biol Chem 281 : 20483–20493. 16714284

34. Koike M, Shibata M, Waguri S, Yoshimura K, Tanida I, et al. (2005) Participation of autophagy in storage of lysosomes in neurons from mouse models of neuronal ceroid-lipofuscinoses (Batten disease). Am J Pathol 167 : 1713–1728. 16314482

35. Settembre C, Fraldi A, Medina DL, Ballabio A (2013) Signals from the lysosome: a control centre for cellular clearance and energy metabolism. Nat Rev Mol Cell Biol 14 : 283–296. doi: 10.1038/nrm3565 23609508

36. Saftig P, Klumperman J (2009) Lysosome biogenesis and lysosomal membrane proteins: trafficking meets function. Nat Rev Mol Cell Biol 10 : 623–635. doi: 10.1038/nrm2745 19672277

37. Yu L, McPhee CK, Zheng L, Mardones GA, Rong Y, et al. (2010) Termination of autophagy and reformation of lysosomes regulated by mTOR. Nature 465 : 942–946. doi: 10.1038/nature09076 20526321

38. Hennings JC, Picard N, Huebner AK, Stauber T, Maier H, et al. (2012) A mouse model for distal renal tubular acidosis reveals a previously unrecognized role of the V-ATPase a4 subunit in the proximal tubule. EMBO Mol Med 4 : 1057–1071. doi: 10.1002/emmm.201201527 22933323

39. Kollmann K, Damme M, Markmann S, Morelle W, Schweizer M, et al. (2012) Lysosomal dysfunction causes neurodegeneration in mucolipidosis II 'knock-in' mice. Brain 135 : 2661–2675. doi: 10.1093/brain/aws209 22961545

40. Rust MB, Faulhaber J, Budack MK, Pfeffer C, Maritzen T, et al. (2006) Neurogenic mechanisms contribute to hypertension in mice with disruption of the K-Cl cotransporter KCC3. Circ Res 98 : 549–556. 16424367

41. Poet M, Kornak U, Schweizer M, Zdebik AA, Scheel O, et al. (2006) Lysosomal storage disease upon disruption of the neuronal chloride transport protein ClC-6. Proc Natl Acad Sci U S A 103 : 13854–13859. 16950870

42. Kankaanpaa P, Paavolainen L, Tiitta S, Karjalainen M, Paivarinne J, et al. (2012) BioImageXD: an open, general-purpose and high-throughput image-processing platform. Nat Methods 9 : 683–689. doi: 10.1038/nmeth.2047 22743773

43. Weinert S, Jabs S, Supanchart C, Schweizer M, Gimber N, et al. (2010) Lysosomal pathology and osteopetrosis upon loss of H+-driven lysosomal Cl -⁠ accumulation. Science 328 : 1401–1403. doi: 10.1126/science.1188072 20430974