Characterization of the complex formed by beta-glucocerebrosidase and the lysosomal integral membrane protein type-2

Zunke F, Andresen L, Wesseler S, Groth J, Arnold P, Rothaug M, Mazzulli JR, Krainc D, Blanz J, Saftig P, Schwake M (2016)
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113(14): 3791-3796.

Download
Es wurde kein Volltext hochgeladen. Nur Publikationsnachweis!
Zeitschriftenaufsatz | Veröffentlicht | Englisch
Autor
; ; ; ; ; ; ; ; ; ;
Abstract / Bemerkung
The lysosomal integral membrane protein type-2 (LIMP-2) plays a pivotal role in the delivery of beta-glucocerebrosidase (GC) to lysosomes. Mutations in GC result in Gaucher's disease (GD) and are the major genetic risk factor for the development of Parkinson's disease (PD). Variants in the LIMP-2 gene cause action myoclonus-renal failure syndrome and also have been linked to PD. Given the importance of GC and LIMP-2 in disease pathogenesis, we studied their interaction sites in more detail. Our previous data demonstrated that the crystal structure of LIMP-2 displays a hydrophobic three-helix bundle composed of helices 4, 5, and 7, of which helix 5 and 7 are important for ligand binding. Here, we identified a similar helical motif in GC through surface potential analysis. Coimmunoprecipitation and immunofluorescence studies revealed a triple-helical interface region within GC as critical for LIMP-2 binding and lysosomal transport. Based on these findings, we generated a LIMP-2 helix 5-derived peptide that precipitated and activated recombinant wild-type and GD-associated N370S mutant GC in vitro. The helix 5 peptide fused to a cell-penetrating peptide also activated endogenous lysosomal GC and reduced alpha-synuclein levels, suggesting that LIMP-2-derived peptides can be used to activate endogenous as well as recombinant wild-type or mutant GC efficiently. Our data also provide a structural model of the LIMP-2/GC complex that will facilitate the development of GC chaperones and activators as potential therapeutics for GD, PD, and related synucleinopathies.
Erscheinungsjahr
Zeitschriftentitel
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Band
113
Ausgabe
14
Seite(n)
3791-3796
ISSN
PUB-ID

Zitieren

Zunke F, Andresen L, Wesseler S, et al. Characterization of the complex formed by beta-glucocerebrosidase and the lysosomal integral membrane protein type-2. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 2016;113(14):3791-3796.
Zunke, F., Andresen, L., Wesseler, S., Groth, J., Arnold, P., Rothaug, M., Mazzulli, J. R., et al. (2016). Characterization of the complex formed by beta-glucocerebrosidase and the lysosomal integral membrane protein type-2. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113(14), 3791-3796. doi:10.1073/pnas.1514005113
Zunke, F., Andresen, L., Wesseler, S., Groth, J., Arnold, P., Rothaug, M., Mazzulli, J. R., Krainc, D., Blanz, J., Saftig, P., et al. (2016). Characterization of the complex formed by beta-glucocerebrosidase and the lysosomal integral membrane protein type-2. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113, 3791-3796.
Zunke, F., et al., 2016. Characterization of the complex formed by beta-glucocerebrosidase and the lysosomal integral membrane protein type-2. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 113(14), p 3791-3796.
F. Zunke, et al., “Characterization of the complex formed by beta-glucocerebrosidase and the lysosomal integral membrane protein type-2”, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, vol. 113, 2016, pp. 3791-3796.
Zunke, F., Andresen, L., Wesseler, S., Groth, J., Arnold, P., Rothaug, M., Mazzulli, J.R., Krainc, D., Blanz, J., Saftig, P., Schwake, M.: Characterization of the complex formed by beta-glucocerebrosidase and the lysosomal integral membrane protein type-2. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA. 113, 3791-3796 (2016).
Zunke, Friederike, Andresen, Lisa, Wesseler, Sophia, Groth, Johann, Arnold, Philipp, Rothaug, Michelle, Mazzulli, Joseph R., Krainc, Dimitri, Blanz, Judith, Saftig, Paul, and Schwake, Michael. “Characterization of the complex formed by beta-glucocerebrosidase and the lysosomal integral membrane protein type-2”. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 113.14 (2016): 3791-3796.

9 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

Dysregulation of the autophagic-lysosomal pathway in Gaucher and Parkinson's disease.
Pitcairn C, Wani WY, Mazzulli JR., Neurobiol Dis 122(), 2019
PMID: 29550539
The role of glucocerebrosidase in Parkinson disease pathogenesis.
Gegg ME, Schapira AHV., FEBS J 285(19), 2018
PMID: 29385658
In vivo regulation of the A disintegrin and metalloproteinase 10 (ADAM10) by the tetraspanin 15.
Seipold L, Altmeppen H, Koudelka T, Tholey A, Kasparek P, Sedlacek R, Schweizer M, Bär J, Mikhaylova M, Glatzel M, Saftig P., Cell Mol Life Sci 75(17), 2018
PMID: 29520422
Exploring genetic modifiers of Gaucher disease: The next horizon.
Davidson BA, Hassan S, Garcia EJ, Tayebi N, Sidransky E., Hum Mutat 39(12), 2018
PMID: 30098107
Stabilization of Glucocerebrosidase by Active Site Occupancy.
Ben Bdira F, Kallemeijn WW, Oussoren SV, Scheij S, Bleijlevens B, Florea BI, van Roomen CPAA, Ottenhoff R, van Kooten MJFM, Walvoort MTC, Witte MD, Boot RG, Ubbink M, Overkleeft HS, Aerts JMFG., ACS Chem Biol 12(7), 2017
PMID: 28485919
Lysosomal integral membrane protein-2 as a phospholipid receptor revealed by biophysical and cellular studies.
Conrad KS, Cheng TW, Ysselstein D, Heybrock S, Hoth LR, Chrunyk BA, Am Ende CW, Krainc D, Schwake M, Saftig P, Liu S, Qiu X, Ehlers MD., Nat Commun 8(1), 2017
PMID: 29199275
Design and Synthesis of Potent Quinazolines as Selective β-Glucocerebrosidase Modulators.
Zheng J, Chen L, Schwake M, Silverman RB, Krainc D., J Med Chem 59(18), 2016
PMID: 27598312
Subcellular Trafficking of Mammalian Lysosomal Proteins: An Extended View.
Staudt C, Puissant E, Boonen M., Int J Mol Sci 18(1), 2016
PMID: 28036022

35 References

Daten bereitgestellt von Europe PubMed Central.

LIMP-2 is a receptor for lysosomal mannose-6-phosphate-independent targeting of beta-glucocerebrosidase.
Reczek D, Schwake M, Schroder J, Hughes H, Blanz J, Jin X, Brondyk W, Van Patten S, Edmunds T, Saftig P., Cell 131(4), 2007
PMID: 18022370
Mannose 6-phosphate-independent Lysosomal Sorting of LIMP-2.
Blanz J, Zunke F, Markmann S, Damme M, Braulke T, Saftig P, Schwake M., Traffic 16(10), 2015
PMID: 26219725
Array-based gene discovery with three unrelated subjects shows SCARB2/LIMP-2 deficiency causes myoclonus epilepsy and glomerulosclerosis.
Berkovic SF, Dibbens LM, Oshlack A, Silver JD, Katerelos M, Vears DF, Lullmann-Rauch R, Blanz J, Zhang KW, Stankovich J, Kalnins RM, Dowling JP, Andermann E, Andermann F, Faldini E, D'Hooge R, Vadlamudi L, Macdonell RA, Hodgson BL, Bayly MA, Savige J, Mulley JC, Smyth GK, Power DA, Saftig P, Bahlo M., Am. J. Hum. Genet. 82(3), 2008
PMID: 18308289
Gaucher disease: mutation and polymorphism spectrum in the glucocerebrosidase gene (GBA).
Hruska KS, LaMarca ME, Scott CR, Sidransky E., Hum. Mutat. 29(5), 2008
PMID: 18338393
A multicenter study of glucocerebrosidase mutations in dementia with Lewy bodies.
Nalls MA, Duran R, Lopez G, Kurzawa-Akanbi M, McKeith IG, Chinnery PF, Morris CM, Theuns J, Crosiers D, Cras P, Engelborghs S, De Deyn PP, Van Broeckhoven C, Mann DM, Snowden J, Pickering-Brown S, Halliwell N, Davidson Y, Gibbons L, Harris J, Sheerin UM, Bras J, Hardy J, Clark L, Marder K, Honig LS, Berg D, Maetzler W, Brockmann K, Gasser T, Novellino F, Quattrone A, Annesi G, De Marco EV, Rogaeva E, Masellis M, Black SE, Bilbao JM, Foroud T, Ghetti B, Nichols WC, Pankratz N, Halliday G, Lesage S, Klebe S, Durr A, Duyckaerts C, Brice A, Giasson BI, Trojanowski JQ, Hurtig HI, Tayebi N, Landazabal C, Knight MA, Keller M, Singleton AB, Wolfsberg TG, Sidransky E., JAMA Neurol 70(6), 2013
PMID: 23588557
Exploring the link between glucocerebrosidase mutations and parkinsonism.
Westbroek W, Gustafson AM, Sidransky E., Trends Mol Med 17(9), 2011
PMID: 21723784
Glucocerebrosidase deficiency in substantia nigra of parkinson disease brains.
Gegg ME, Burke D, Heales SJ, Cooper JM, Hardy J, Wood NW, Schapira AH., Ann. Neurol. 72(3), 2012
PMID: 23034917
LIMP-2 expression is critical for β-glucocerebrosidase activity and α-synuclein clearance.
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., Proc. Natl. Acad. Sci. U.S.A. 111(43), 2014
PMID: 25316793
Genetic analysis implicates APOE, SNCA and suggests lysosomal dysfunction in the etiology of dementia with Lewy bodies.
Bras J, Guerreiro R, Darwent L, Parkkinen L, Ansorge O, Escott-Price V, Hernandez DG, Nalls MA, Clark LN, Honig LS, Marder K, Van Der Flier WM, Lemstra A, Scheltens P, Rogaeva E, St George-Hyslop P, Londos E, Zetterberg H, Ortega-Cubero S, Pastor P, Ferman TJ, Graff-Radford NR, Ross OA, Barber I, Braae A, Brown K, Morgan K, Maetzler W, Berg D, Troakes C, Al-Sarraj S, Lashley T, Compta Y, Revesz T, Lees A, Cairns N, Halliday GM, Mann D, Pickering-Brown S, Dickson DW, Singleton A, Hardy J., Hum. Mol. Genet. 23(23), 2014
PMID: 24973356
CNS expression of glucocerebrosidase corrects alpha-synuclein pathology and memory in a mouse model of Gaucher-related synucleinopathy.
Sardi SP, Clarke J, Kinnecom C, Tamsett TJ, Li L, Stanek LM, Passini MA, Grabowski GA, Schlossmacher MG, Sidman RL, Cheng SH, Shihabuddin LS., Proc. Natl. Acad. Sci. U.S.A. 108(29), 2011
PMID: 21730160
Augmenting CNS glucocerebrosidase activity as a therapeutic strategy for parkinsonism and other Gaucher-related synucleinopathies.
Sardi SP, Clarke J, Viel C, Chan M, Tamsett TJ, Treleaven CM, Bu J, Sweet L, Passini MA, Dodge JC, Yu WH, Sidman RL, Cheng SH, Shihabuddin LS., Proc. Natl. Acad. Sci. U.S.A. 110(9), 2013
PMID: 23297226
Glucocerebrosidase is shaking up the synucleinopathies.
Siebert M, Sidransky E, Westbroek W., Brain 137(Pt 5), 2014
PMID: 24531622
Gaucher disease glucocerebrosidase and α-synuclein form a bidirectional pathogenic loop in synucleinopathies.
Mazzulli JR, Xu YH, Sun Y, Knight AL, McLean PJ, Caldwell GA, Sidransky E, Grabowski GA, Krainc D., Cell 146(1), 2011
PMID: 21700325
Structure of LIMP-2 provides functional insights with implications for SR-BI and CD36.
Neculai D, Schwake M, Ravichandran M, Zunke F, Collins RF, Peters J, Neculai M, Plumb J, Loppnau P, Pizarro JC, Seitova A, Trimble WS, Saftig P, Grinstein S, Dhe-Paganon S., Nature 504(7478), 2013
PMID: 24162852
Structural comparison of differently glycosylated forms of acid-beta-glucosidase, the defective enzyme in Gaucher disease.
Brumshtein B, Wormald MR, Silman I, Futerman AH, Sussman JL., Acta Crystallogr. D Biol. Crystallogr. 62(Pt 12), 2006
PMID: 17139081
X-ray structure of human acid-beta-glucosidase, the defective enzyme in Gaucher disease.
Dvir H, Harel M, McCarthy AA, Toker L, Silman I, Futerman AH, Sussman JL., EMBO Rep. 4(7), 2003
PMID: 12792654
Mutation analysis of Gaucher disease patients from Argentina: high prevalence of the RecNciI mutation.
Cormand B, Harboe TL, Gort L, Campoy C, Blanco M, Chamoles N, Chabas A, Vilageliu L, Grinberg D., Am. J. Med. Genet. 80(4), 1998
PMID: 9856561
Lysosome sorting of β-glucocerebrosidase by LIMP-2 is targeted by the mannose 6-phosphate receptor.
Zhao Y, Ren J, Padilla-Parra S, Fry EE, Stuart DI., Nat Commun 5(), 2014
PMID: 25027712
Extracellular Juxtamembrane Segment of ADAM17 Interacts with Membranes and Is Essential for Its Shedding Activity.
Dusterhoft S, Michalek M, Kordowski F, Oldefest M, Sommer A, Roseler J, Reiss K, Grotzinger J, Lorenzen I., Biochemistry 54(38), 2015
PMID: 26348730
Import into and degradation of cytosolic proteins by isolated yeast vacuoles.
Horst M, Knecht EC, Schu PV., Mol. Biol. Cell 10(9), 1999
PMID: 10473633
α-Synuclein-induced lysosomal dysfunction occurs through disruptions in protein trafficking in human midbrain synucleinopathy models.
Mazzulli JR, Zunke F, Isacson O, Studer L, Krainc D., Proc. Natl. Acad. Sci. U.S.A. 113(7), 2016
PMID: 26839413
Analyses of variant acid beta-glucosidases: effects of Gaucher disease mutations.
Liou B, Kazimierczuk A, Zhang M, Scott CR, Hegde RS, Grabowski GA., J. Biol. Chem. 281(7), 2005
PMID: 16293621
Receptor-mediated uptake of lysosomal enzymes.
Sly WS, Kaplan A, Achord DT, Brot FE, Bell CE., Prog. Clin. Biol. Res. 23(), 1978
PMID: 662919
Evidence for receptor-mediated binding of glycoproteins, glycoconjugates, and lysosomal glycosidases by alveolar macrophages.
Stahl PD, Rodman JS, Miller MJ, Schlesinger PH., Proc. Natl. Acad. Sci. U.S.A. 75(3), 1978
PMID: 274729
Therapeutic goals in the treatment of Gaucher disease.
Pastores GM, Weinreb NJ, Aerts H, Andria G, Cox TM, Giralt M, Grabowski GA, Mistry PK, Tylki-Szymanska A., Semin. Hematol. 41(4 Suppl 5), 2004
PMID: 15468045
Pharmacological chaperone therapy for Gaucher disease: a patent review.
Benito JM, Garcia Fernandez JM, Ortiz Mellet C., Expert Opin Ther Pat 21(6), 2011
PMID: 21457079
Discovery, structure-activity relationship, and biological evaluation of noninhibitory small molecule chaperones of glucocerebrosidase.
Patnaik S, Zheng W, Choi JH, Motabar O, Southall N, Westbroek W, Lea WA, Velayati A, Goldin E, Sidransky E, Leister W, Marugan JJ., J. Med. Chem. 55(12), 2012
PMID: 22646221
DETERMINATION OF THE COEFFICIENT OF CORRELATION.
Pearson K., Science 30(757), 1909
PMID: 17838275

Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®

Quellen

PMID: 27001828
PubMed | Europe PMC

Suchen in

Google Scholar