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Acta Neuropathologica Communications
Published in: Acta Neuropathologica Communications 1/2015

Open Access 01-12-2015 | Research

LAMP-2 deficiency leads to hippocampal dysfunction but normal clearance of neuronal substrates of chaperone-mediated autophagy in a mouse model for Danon disease

Authors: Michelle Rothaug, Stijn Stroobants, Michaela Schweizer, Judith Peters, Friederike Zunke, Mirka Allerding, Rudi D’Hooge, Paul Saftig, Judith Blanz

Published in: Acta Neuropathologica Communications | Issue 1/2015

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Abstract

The Lysosomal Associated Membrane Protein type-2 (LAMP-2) is an abundant lysosomal membrane protein with an important role in immunity, macroautophagy (MA) and chaperone-mediated autophagy (CMA). Mutations within the Lamp2 gene cause Danon disease, an X-linked lysosomal storage disorder characterized by (cardio)myopathy and intellectual dysfunction. The pathological hallmark of this disease is an accumulation of glycogen and autophagic vacuoles in cardiac and skeletal muscle that, along with the myopathy, is also present in LAMP-2-deficient mice. Intellectual dysfunction observed in the human disease suggests a pivotal role of LAMP-2 within brain. LAMP-2A, one specific LAMP-2 isoform, was proposed to be important for the lysosomal degradation of selective proteins involved in neurodegenerative diseases such as Huntington’s and Parkinson’s disease.
To elucidate the neuronal function of LAMP-2 we analyzed knockout mice for neuropathological changes, MA and steady-state levels of CMA substrates. The absence of LAMP-2 in murine brain led to inflammation and abnormal behavior, including motor deficits and impaired learning. The latter abnormality points to hippocampal dysfunction caused by altered lysosomal activity, distinct accumulation of p62-positive aggregates, autophagic vacuoles and lipid storage within hippocampal neurons and their presynaptic terminals. The absence of LAMP-2 did not apparently affect MA or steady-state levels of selected CMA substrates in brain or neuroblastoma cells under physiological and prolonged starvation conditions.
Our data contribute to the understanding of intellectual dysfunction observed in Danon disease patients and highlight the role of LAMP-2 within the central nervous system, particularly the hippocampus.
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Literature
1.
Wilke S, Krausze J, Bussow K (2012) Crystal structure of the conserved domain of the DC lysosomal associated membrane protein: implications for the lysosomal glycocalyx. BMC Biol 10:62. doi:10.1186/1741-7007-10-62
2.
Neiss WF (1984) A coat of glycoconjugates on the inner surface of the lysosomal membrane in the rat kidney. Histochemistry 80(6):603–608PubMedCrossRef
3.
Kundra R, Kornfeld S (1999) Asparagine-linked oligosaccharides protect Lamp-1 and Lamp-2 from intracellular proteolysis. J Biol Chem 274(43):31039–31046PubMedCrossRef
4.
Tanaka Y, Guhde G, Suter A, Eskelinen EL, Hartmann D, Lullmann-Rauch R, Janssen PM, Blanz J, von Figura K, Saftig P (2000) Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature 406(6798):902–906, doi:10.1038/35022595PubMedCrossRef
5.
Eskelinen EL (2006) Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy. Mol Aspects Med 27(5–6):495–502, doi:10.1016/j.mam.2006.08.005PubMedCrossRef
6.
Beertsen W, Willenborg M, Everts V, Zirogianni A, Podschun R, Schroder B, Eskelinen EL, Saftig P (2008) Impaired phagosomal maturation in neutrophils leads to periodontitis in lysosomal-associated membrane protein-2 knockout mice. J Immunol 180(1):475–482PubMedCrossRef
7.
Binker MG, Cosen-Binker LI, Terebiznik MR, Mallo GV, McCaw SE, Eskelinen EL, Willenborg M, Brumell JH, Saftig P, Grinstein S, Gray-Owen SD (2007) Arrested maturation of Neisseria-containing phagosomes in the absence of the lysosome-associated membrane proteins, LAMP-1 and LAMP-2. Cell Microbiol 9(9):2153–2166, doi:10.1111/j.1462-5822.2007.00946PubMedCrossRef
8.
Huynh KK, Eskelinen EL, Scott CC, Malevanets A, Saftig P, Grinstein S (2007) LAMP proteins are required for fusion of lysosomes with phagosomes. EMBO J 26(2):313–324, doi:10.1038/sj.emboj.7601511PubMedCentralPubMedCrossRef
9.
Eskelinen EL, Schmidt CK, Neu S, Willenborg M, Fuertes G, Salvador N, Tanaka Y, Lullmann-Rauch R, Hartmann D, Heeren J, von Figura K, Knecht E, Saftig P (2004) Disturbed cholesterol traffic but normal proteolytic function in LAMP-1/LAMP-2 double-deficient fibroblasts. Mol Biol Cell 15(7):3132–3145, doi:10.1091/mbc.E04-02-0103E04-02-0103PubMedCentralPubMedCrossRef
10.
Schneede A, Schmidt CK, Holtta-Vuori M, Heeren J, Willenborg M, Blanz J, Domanskyy M, Breiden B, Brodesser S, Landgrebe J, Sandhoff K, Ikonen E, Saftig P, Eskelinen EL (2011) Role for LAMP-2 in endosomal cholesterol transport. J Cell Mol Med 15(2):280–295, doi:10.1111/j.1582-4934.2009PubMedCrossRef
11.
Konecki DS, Foetisch K, Zimmer KP, Schlotter M, Lichter-Konecki U (1995) An alternatively spliced form of the human lysosome-associated membrane protein-2 gene is expressed in a tissue-specific manner. Biochem Biophys Res Commun 215(2):757–767PubMedCrossRef
12.
Hatem CL, Gough NR, Fambrough DM (1995) Multiple mRNAs encode the avian lysosomal membrane protein LAMP-2, resulting in alternative transmembrane and cytoplasmic domains. J Cell Sci 108(Pt 5):2093–2100PubMed
13.
Lichter-Konecki U, Moter SE, Krawisz BR, Schlotter M, Hipke C, Konecki DS (1999) Expression patterns of murine lysosome-associated membrane protein 2 (Lamp-2) transcripts during morphogenesis. Differentiation 65(1):43–58, doi:10.1046/j.1432-0436.1999.6510043PubMedCrossRef
14.
Cuervo AM, Dice JF (1996) A receptor for the selective uptake and degradation of proteins by lysosomes. Science 273(5274):501–503PubMedCrossRef
15.
Cuervo AM, Dice JF (2000) Unique properties of lamp2a compared to other lamp2 isoforms. J Cell Sci 113(Pt 24):4441–4450PubMed
16.
17.
Zhou D, Li P, Lin Y, Lott JM, Hislop AD, Canaday DH, Brutkiewicz RR, Blum JS (2005) Lamp-2a facilitates MHC class II presentation of cytoplasmic antigens. Immunity 22(5):571–581, doi:10.1016/j.immuni.2005.03.009PubMedCrossRef
18.
Valdor R, Mocholi E, Botbol Y, Guerrero-Ros I, Chandra D, Koga H, Gravekamp C, Cuervo AM, Macian F (2014) Chaperone-mediated autophagy regulates T cell responses through targeted degradation of negative regulators of T cell activation. Nat Immunol. doi:10.1038/ni.3003
19.
Cuervo AM, Stefanis L, Fredenburg R, Lansbury PT, Sulzer D (2004) Impaired degradation of mutant alpha-synuclein by chaperone-mediated autophagy. Science 305(5688):1292–1295, doi:10.1126/science.1101738305/5688/1292PubMedCrossRef
20.
Xilouri M, Brekk OR, Landeck N, Pitychoutis PM, Papasilekas T, Papadopoulou-Daifoti Z, Kirik D, Stefanis L (2013) Boosting chaperone-mediated autophagy in vivo mitigates alpha-synuclein-induced neurodegeneration. Brain 136(Pt 7):2130–2146, doi:10.1093/brain/awt131 awt131PubMedCrossRef
21.
Koga H, Cuervo AM (2011) Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration. Neurobiol Dis 43(1):29–37, doi:10.1016/j.nbd.2010.07.006PubMedCentralPubMedCrossRef
22.
Qi L, Zhang XD, Wu JC, Lin F, Wang J, DiFiglia M, Qin ZH (2012) The role of chaperone-mediated autophagy in huntingtin degradation. PLoS One 7(10):e46834, doi:10.1371/journal.pone.0046834PubMedCentralPubMedCrossRef
23.
Tobin AJ, Signer ER (2000) Huntington’s disease: the challenge for cell biologists. Trends Cell Biol 10(12):531–536PubMedCrossRef
24.
Periquet M, Fulga T, Myllykangas L, Schlossmacher MG, Feany MB (2007) Aggregated alpha-synuclein mediates dopaminergic neurotoxicity in vivo. J Neurosci 27(12):3338–3346, doi:10.1523/JNEUROSCI.0285-07.2007PubMedCrossRef
25.
Danon MJ, Oh SJ, DiMauro S, Manaligod JR, Eastwood A, Naidu S, Schliselfeld LH (1981) Lysosomal glycogen storage disease with normal acid maltase. Neurology 31(1):51–57PubMedCrossRef
26.
Nishino I, Fu J, Tanji K, Yamada T, Shimojo S, Koori T, Mora M, Riggs JE, Oh SJ, Koga Y, Sue CM, Yamamoto A, Murakami N, Shanske S, Byrne E, Bonilla E, Nonaka I, DiMauro S, Hirano M (2000) Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease). Nature 406(6798):906–910, doi:10.1038/35022604PubMedCrossRef
27.
Cheng Z, Fang Q (2012) Danon disease: focusing on heart. J Hum Genet 57(7):407–410, doi:10.1038/jhg.2012.72PubMedCrossRef
28.
Stypmann J, Janssen PM, Prestle J, Engelen MA, Kogler H, Lullmann-Rauch R, Eckardt L, von Figura K, Landgrebe J, Mleczko A, Saftig P (2006) LAMP-2 deficient mice show depressed cardiac contractile function without significant changes in calcium handling. Basic Res Cardiol 101(4):281–291, doi:10.1007/s00395-006-0591-6PubMedCrossRef
29.
Furuta A, Wakabayashi K, Haratake J, Kikuchi H, Kabuta T, Mori F, Tokonami F, Katsumi Y, Tanioka F, Uchiyama Y, Nishino I, Wada K (2013) Lysosomal storage and advanced senescence in the brain of LAMP-2-deficient Danon disease. Acta Neuropathol 125(3):459–461, doi:10.1007/s00401-012-1075-4PubMedCrossRef
30.
Saftig P, Tanaka Y, Lullmann-Rauch R, von Figura K (2001) Disease model: LAMP-2 enlightens Danon disease. Trends Mol Med 7(1):37–39PubMedCrossRef
31.
Hsu CY, Uludag H (2012) A simple and rapid nonviral approach to efficiently transfect primary tissue-derived cells using polyethylenimine. Nat Protoc 7(5):935–945, doi:10.1038/nprot.2012.038PubMedCrossRef
32.
Naert A, Callaerts-Vegh Z, Moechars D, Meert T, D'Hooge R (2011) Vglut2 haploinsufficiency enhances behavioral sensitivity to MK-801 and amphetamine in mice. Prog Neuropsychopharmacol Biol Psychiatry 35(5):1316–1321, doi:10.1016/j.pnpbp.2011.03.023PubMedCrossRef
33.
Blanz J, Stroobants S, Lullmann-Rauch R, Morelle W, Ludemann M, D'Hooge R, Reuterwall H, Michalski JC, Fogh J, Andersson C, Saftig P (2008) Reversal of peripheral and central neural storage and ataxia after recombinant enzyme replacement therapy in alpha-mannosidosis mice. Hum Mol Genet 17(22):3437–3445, doi:10.1093/hmg/ddn237PubMedCrossRef
34.
Dobrenis K, Chang HY, Pina-Benabou MH, Woodroffe A, Lee SC, Rozental R, Spray DC, Scemes E (2005) Human and mouse microglia express connexin36, and functional gap junctions are formed between rodent microglia and neurons. J Neurosci Res 82(3):306–315, doi:10.1002/jnr.20650PubMedCentralPubMedCrossRef
35.
36.
Rothaug M, Zunke F, Mazzulli JR, Schweizer M, Altmeppen H, Lullmann-Rauch R, Kallemeijn WW, Gaspar P, Aerts JM, Glatzel M, Saftig P, Krainc D, Schwake M, Blanz J (2014) LIMP-2 expression is critical for beta-glucocerebrosidase activity and alpha-synuclein clearance. Proc Natl Acad Sci U S A 111(43):15573–15578, doi:10.1073/pnas.1405700111PubMedCrossRef
37.
Fujiwara Y, Furuta A, Kikuchi H, Aizawa S, Hatanaka Y, Konya C, Uchida K, Yoshimura A, Tamai Y, Wada K, Kabuta T (2013) Discovery of a novel type of autophagy targeting RNA. Autophagy 9(3):403–409, doi:10.4161/auto.2300223002PubMedCentralPubMedCrossRef
38.
Henell F, Berkenstam A, Ahlberg J, Glaumann H (1987) Degradation of short- and long-lived proteins in perfused liver and in isolated autophagic vacuoles--lysosomes. Exp Mol Pathol 46(1):1–14PubMedCrossRef
39.
Komatsu M, Waguri S, Koike M, Sou YS, Ueno T, Hara T, Mizushima N, Iwata J, Ezaki J, Murata S, Hamazaki J, Nishito Y, Iemura S, Natsume T, Yanagawa T, Uwayama J, Warabi E, Yoshida H, Ishii T, Kobayashi A, Yamamoto M, Yue Z, Uchiyama Y, Kominami E, Tanaka K (2007) Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131(6):1149–1163, doi:10.1016/j.cell.2007.10.035PubMedCrossRef
40.
Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T (2007) p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 282(33):24131–24145, doi:10.1074/jbc.M702824200PubMedCrossRef
41.
Jolly RD, Walkley SU (1997) Lysosomal storage diseases of animals: an essay in comparative pathology. Vet Pathol 34(6):527–548PubMedCrossRef
42.
Wang L, Harris TE, Lawrence JC Jr (2008) Regulation of proline-rich Akt substrate of 40 kDa (PRAS40) function by mammalian target of rapamycin complex 1 (mTORC1)-mediated phosphorylation. J Biol Chem 283(23):15619–15627, doi:10.1074/jbc.M800723200PubMedCentralPubMedCrossRef
43.
Sancak Y, Thoreen CC, Peterson TR, Lindquist RA, Kang SA, Spooner E, Carr SA, Sabatini DM (2007) PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol Cell 25(6):903–915, doi:10.1016/j.molcel.2007.03.003PubMedCrossRef
44.
Yang Q, She H, Gearing M, Colla E, Lee M, Shacka JJ, Mao Z (2009) Regulation of neuronal survival factor MEF2D by chaperone-mediated autophagy. Science 323(5910):124–127, doi:10.1126/science.1166088 323/5910/124PubMedCentralPubMedCrossRef
45.
46.
Settembre C, De Cegli R, Mansueto G, Saha PK, Vetrini F, Visvikis O, Huynh T, Carissimo A, Palmer D, Klisch TJ, Wollenberg AC, Di Bernardo D, Chan L, Irazoqui JE, Ballabio A (2013) TFEB controls cellular lipid metabolism through a starvation-induced autoregulatory loop. Nat Cell Biol 15(6):647–658, doi:10.1038/ncb2718PubMedCentralPubMedCrossRef
47.
Vogiatzi T, Xilouri M, Vekrellis K, Stefanis L (2008) Wild type alpha-synuclein is degraded by chaperone-mediated autophagy and macroautophagy in neuronal cells. J Biol Chem 283(35):23542–23556, doi:10.1074/jbc.M801992200PubMedCentralPubMedCrossRef
48.
Kasper D, Planells-Cases R, Fuhrmann JC, Scheel O, Zeitz O, Ruether K, Schmitt A, Poet M, Steinfeld R, Schweizer M, Kornak U, Jentsch TJ (2005) Loss of the chloride channel ClC-7 leads to lysosomal storage disease and neurodegeneration. EMBO J 24(5):1079–1091, doi:10.1038/sj.emboj.7600576PubMedCentralPubMedCrossRef
49.
Mitchison HM, Lim MJ, Cooper JD (2004) Selectivity and types of cell death in the neuronal ceroid lipofuscinoses. Brain Pathol 14(1):86–96PubMedCrossRef
50.
Zhu H, Yoshimoto T, Imajo-Ohmi S, Dazortsava M, Mathivanan A, Yamashima T (2012) Why are hippocampal CA1 neurons vulnerable but motor cortex neurons resistant to transient ischemia? J Neurochem 120(4):574–585, doi:10.1111/j.1471-4159.2011.07550.xPubMedCrossRef
51.
Kirkegaard T, Roth AG, Petersen NH, Mahalka AK, Olsen OD, Moilanen I, Zylicz A, Knudsen J, Sandhoff K, Arenz C, Kinnunen PK, Nylandsted J, Jaattela M (2010) Hsp70 stabilizes lysosomes and reverts Niemann-Pick disease-associated lysosomal pathology. Nature 463(7280):549–553, doi:10.1038/nature08710PubMedCrossRef
52.
Nylandsted J, Gyrd-Hansen M, Danielewicz A, Fehrenbacher N, Lademann U, Hoyer-Hansen M, Weber E, Multhoff G, Rohde M, Jaattela M (2004) Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. The Journal of experimental medicine 200(4):425–435, doi:10.1084/jem.20040531 jem.20040531PubMedCentralPubMedCrossRef
53.
Saha T (2012) LAMP2A overexpression in breast tumors promotes cancer cell survival via chaperone-mediated autophagy. Autophagy 8(11):1643–1656, doi:10.4161/auto.21654PubMedCentralPubMedCrossRef
54.
Boucek D, Jirikowic J, Taylor M (2011) Natural history of Danon disease. Genet Med 13(6):563–568, doi:10.1097/GIM.0b013e31820ad795PubMedCrossRef
55.
Taylor MR, Ku L, Slavov D, Cavanaugh J, Boucek M, Zhu X, Graw S, Carniel E, Barnes C, Quan D, Prall R, Lovell MA, Mierau G, Ruegg P, Mandava N, Bristow MR, Towbin JA, Mestroni L (2007) Danon disease presenting with dilated cardiomyopathy and a complex phenotype. J Hum Genet 52(10):830–835, doi:10.1007/s10038-007-0184-8PubMedCrossRef
56.
Bandyopadhyay U, Sridhar S, Kaushik S, Kiffin R, Cuervo AM (2010) Identification of regulators of chaperone-mediated autophagy. Mol Cell 39(4):535–547, doi:10.1016/j.molcel.2010.08.004S1097-2765(10)00614-3PubMedCentralPubMedCrossRef
57.
Wolfsdorf JI, Weinstein DA (2003) Glycogen storage diseases. Rev Endocr Metab Disord 4(1):95–102, doi:5109165PubMedCrossRef
58.
Malicdan MC, Noguchi S, Nonaka I, Saftig P, Nishino I (2008) Lysosomal myopathies: an excessive build-up in autophagosomes is too much to handle. Neuromuscul Disord 18(7):521–529, doi:10.1016/j.nmd.2008.04.010 S0960-8966(08)00106-5PubMedCrossRef
59.
Eskelinen EL, Illert AL, Tanaka Y, Schwarzmann G, Blanz J, Von Figura K, Saftig P (2002) Role of LAMP-2 in lysosome biogenesis and autophagy. Mol Biol Cell 13(9):3355–3368, doi:10.1091/mbc.E02-02-0114PubMedCentralPubMedCrossRef
60.
Criado O, Aguado C, Gayarre J, Duran-Trio L, Garcia-Cabrero AM, Vernia S, San Millan B, Heredia M, Roma-Mateo C, Mouron S, Juana-Lopez L, Dominguez M, Navarro C, Serratosa JM, Sanchez M, Sanz P, Bovolenta P, Knecht E, Rodriguez De Cordoba S (2012) Lafora bodies and neurological defects in malin-deficient mice correlate with impaired autophagy. Hum Mol Genet 21(7):1521–1533, doi:10.1093/hmg/ddr590ddr590PubMedCrossRef
61.
Puri R, Suzuki T, Yamakawa K, Ganesh S (2012) Dysfunctions in endosomal-lysosomal and autophagy pathways underlie neuropathology in a mouse model for Lafora disease. Hum Mol Genet 21(1):175–184, doi:10.1093/hmg/ddr452PubMedCrossRef
62.
Valles-Ortega J, Duran J, Garcia-Rocha M, Bosch C, Saez I, Pujadas L, Serafin A, Canas X, Soriano E, Delgado-Garcia JM, Gruart A, Guinovart JJ (2011) Neurodegeneration and functional impairments associated with glycogen synthase accumulation in a mouse model of Lafora disease. EMBO Mol Med 3(11):667–681, doi:10.1002/emmm.201100174PubMedCentralPubMedCrossRef
63.
64.
Thompson LM, Aiken CT, Kaltenbach LS, Agrawal N, Illes K, Khoshnan A, Martinez-Vincente M, Arrasate M, O'Rourke JG, Khashwji H, Lukacsovich T, Zhu YZ, Lau AL, Massey A, Hayden MR, Zeitlin SO, Finkbeiner S, Green KN, LaFerla FM, Bates G, Huang L, Patterson PH, Lo DC, Cuervo AM, Marsh JL, Steffan JS (2009) IKK phosphorylates Huntingtin and targets it for degradation by the proteasome and lysosome. The Journal of cell biology 187(7):1083–1099, doi:10.1083/jcb.200909067PubMedCentralPubMedCrossRef
65.
Koga H, Martinez-Vicente M, Arias E, Kaushik S, Sulzer D, Cuervo AM (2011) Constitutive upregulation of chaperone-mediated autophagy in Huntington's disease. J Neurosci 31(50):18492–18505, doi:10.1523/JNEUROSCI. 3219-11.2011PubMedCentralPubMedCrossRef
66.
Massey AC, Kaushik S, Sovak G, Kiffin R, Cuervo AM (2006) Consequences of the selective blockage of chaperone-mediated autophagy. Proc Natl Acad Sci U S A 103 (15):5805-5810. doi:0507436103
67.
68.
Zhang C, Cuervo AM (2008) Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nature medicine 14(9):959–965, doi:10.1038/nm.1851PubMedCentralPubMedCrossRef
69.
Sardiello M, Palmieri M, di Ronza A, Medina DL, Valenza M, Gennarino VA, Di Malta C, Donaudy F, Embrione V, Polishchuk RS, Banfi S, Parenti G, Cattaneo E, Ballabio A (2009) A gene network regulating lysosomal biogenesis and function. Science 325(5939):473–477, doi:10.1126/science.1174447PubMed
Metadata
Title
LAMP-2 deficiency leads to hippocampal dysfunction but normal clearance of neuronal substrates of chaperone-mediated autophagy in a mouse model for Danon disease
Authors
Michelle Rothaug
Stijn Stroobants
Michaela Schweizer
Judith Peters
Friederike Zunke
Mirka Allerding
Rudi D’Hooge
Paul Saftig
Judith Blanz
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Acta Neuropathologica Communications / Issue 1/2015
Electronic ISSN: 2051-5960
DOI
https://doi.org/10.1186/s40478-014-0182-y

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