Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites.

Brodehl A, Stanasiuk C, Anselmetti D, Gummert J, Milting H (2019)
FEBS open bio 9(4): 996-1007.

Zeitschriftenaufsatz | E-Veröff. vor dem Druck | Englisch
 
Download
Es wurden keine Dateien hochgeladen. Nur Publikationsnachweis!
Autor*in
Brodehl, Andreas; Stanasiuk, Caroline; Anselmetti, DarioUniBi ; Gummert, Jan; Milting, Hendrik
Abstract / Bemerkung
Desmocollin-2 (DSC2) is a desmosomal protein of the cadherin family. Desmosomes are multiprotein complexes, which are involved in cell adhesion of cardiomyocytes and of keratinocytes. The molecular structure of the complete extracellular domain (ECD) of DSC2 was recently described, revealing three disulfide bridges, four N-glycosylation sites, and four O-mannosylation sites. However, the functional relevance of these post-translational modifications for the protein trafficking of DSC2 to the plasma membrane is still unknown. Here, we generated a set of DSC2 mutants, in which we systematically exchanged all N-glycosylation sites, O-mannosylation sites, and disulfide bridges within the ECD and investigated the resulting subcellular localization by confocal laser scanning microscopy. Of note, all single and double N-glycosylation- deficient mutants were efficiently incorporated into the plasma membrane, indicating that the absence of these glycosylation sites has a minor effect on the protein trafficking of DSC2. However, the exchange of multiple N-glycosylation sites resulted in intracellular accumulation. Colocalization analysis using cell compartment trackers revealed that N-glycosylation- deficient DSC2 mutants were retained within the Golgi apparatus. In contrast, elimination of the four O-mannosylation sites or the disulfide bridges in the ECD has no obvious effect on the intracellular protein processing of DSC2. These experiments underscore the importance of N-glycosylation at multiple sites of DSC2 for efficient intracellular transport to the plasma membrane. © 2019 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.
Erscheinungsjahr
2019
Zeitschriftentitel
FEBS open bio
Band
9
Ausgabe
4
Seite(n)
996-1007
ISSN
2211-5463
eISSN
2211-5463
Page URI
https://pub.uni-bielefeld.de/record/2934795

Zitieren

Brodehl A, Stanasiuk C, Anselmetti D, Gummert J, Milting H. Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites. FEBS open bio. 2019;9(4):996-1007.
Brodehl, A., Stanasiuk, C., Anselmetti, D., Gummert, J., & Milting, H. (2019). Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites. FEBS open bio, 9(4), 996-1007. doi:10.1002/2211-5463.12631
Brodehl, Andreas, Stanasiuk, Caroline, Anselmetti, Dario, Gummert, Jan, and Milting, Hendrik. 2019. “Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites.”. FEBS open bio 9 (4): 996-1007.
Brodehl, A., Stanasiuk, C., Anselmetti, D., Gummert, J., and Milting, H. (2019). Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites. FEBS open bio 9, 996-1007.
Brodehl, A., et al., 2019. Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites. FEBS open bio, 9(4), p 996-1007.
A. Brodehl, et al., “Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites.”, FEBS open bio, vol. 9, 2019, pp. 996-1007.
Brodehl, A., Stanasiuk, C., Anselmetti, D., Gummert, J., Milting, H.: Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites. FEBS open bio. 9, 996-1007 (2019).
Brodehl, Andreas, Stanasiuk, Caroline, Anselmetti, Dario, Gummert, Jan, and Milting, Hendrik. “Incorporation of desmocollin-2 into the plasma membrane requires N-glycosylation at multiple sites.”. FEBS open bio 9.4 (2019): 996-1007.

34 References

Daten bereitgestellt von Europe PubMed Central.

Desmosomes in the heart: a review of clinical and mechanistic analyses.
Patel DM, Green KJ., Cell Commun. Adhes. 21(3), 2014
PMID: 24754498
Striate palmoplantar keratoderma: Report of a novel DSG1 mutation and atypical clinical manifestations.
Nomura T, Mizuno O, Miyauchi T, Suzuki S, Shinkuma S, Hata H, Fujita Y, Akiyama M, Shimizu H., J. Dermatol. Sci. 80(3), 2015
PMID: 26493105
Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease).
McKoy G, Protonotarios N, Crosby A, Tsatsopoulou A, Anastasakis A, Coonar A, Norman M, Baboonian C, Jeffery S, McKenna WJ., Lancet 355(9221), 2000
PMID: 10902626
Recessive mutation in desmoplakin disrupts desmoplakin-intermediate filament interactions and causes dilated cardiomyopathy, woolly hair and keratoderma.
Norgett EE, Hatsell SJ, Carvajal-Huerta L, Cabezas JC, Common J, Purkis PE, Whittock N, Leigh IM, Stevens HP, Kelsell DP., Hum. Mol. Genet. 9(18), 2000
PMID: 11063735
De novo desmin-mutation N116S is associated with arrhythmogenic right ventricular cardiomyopathy.
Klauke B, Kossmann S, Gaertner A, Brand K, Stork I, Brodehl A, Dieding M, Walhorn V, Anselmetti D, Gerdes D, Bohms B, Schulz U, Zu Knyphausen E, Vorgerd M, Gummert J, Milting H., Hum. Mol. Genet. 19(23), 2010
PMID: 20829228
Mutations in the desmosomal protein plakophilin-2 are common in arrhythmogenic right ventricular cardiomyopathy.
Gerull B, Heuser A, Wichter T, Paul M, Basson CT, McDermott DA, Lerman BB, Markowitz SM, Ellinor PT, MacRae CA, Peters S, Grossmann KS, Drenckhahn J, Michely B, Sasse-Klaassen S, Birchmeier W, Dietz R, Breithardt G, Schulze-Bahr E, Thierfelder L., Nat. Genet. 36(11), 2004
PMID: 15489853
Genetics of and pathogenic mechanisms in arrhythmogenic right ventricular cardiomyopathy.
Vimalanathan AK, Ehler E, Gehmlich K., Biophys Rev 10(4), 2018
PMID: 29995277
An updated review on the clinicopathologic aspects of arrhythmogenic right ventricular cardiomyopathy.
El Demellawy D, Nasr A, Alowami S., Am J Forensic Med Pathol 30(1), 2009
PMID: 19237863
Compound and digenic heterozygosity contributes to arrhythmogenic right ventricular cardiomyopathy.
Xu T, Yang Z, Vatta M, Rampazzo A, Beffagna G, Pilichou K, Pillichou K, Scherer SE, Saffitz J, Kravitz J, Zareba W, Danieli GA, Lorenzon A, Nava A, Bauce B, Thiene G, Basso C, Calkins H, Gear K, Marcus F, Towbin JA; Multidisciplinary Study of Right Ventricular Dysplasia Investigators., J. Am. Coll. Cardiol. 55(6), 2010
PMID: 20152563
Structural basis of adhesive binding by desmocollins and desmogleins.
Harrison OJ, Brasch J, Lasso G, Katsamba PS, Ahlsen G, Honig B, Shapiro L., Proc. Natl. Acad. Sci. U.S.A. 113(26), 2016
PMID: 27298358
Desmosomal cadherins: another growing multigene family of adhesion molecules.
Koch PJ, Franke WW., Curr. Opin. Cell Biol. 6(5), 1994
PMID: 7833048
Structures of two intermediate filament-binding fragments of desmoplakin reveal a unique repeat motif structure.
Choi HJ, Park-Snyder S, Pascoe LT, Green KJ, Weis WI., Nat. Struct. Biol. 9(8), 2002
PMID: 12101406
The structure of a glycopeptide isolated from the yeast cell wall.
Sentandreu R, Northcote DH., Biochem. J. 109(3), 1968
PMID: 5685868
Discovery of an O-mannosylation pathway selectively serving cadherins and protocadherins.
Larsen ISB, Narimatsu Y, Joshi HJ, Siukstaite L, Harrison OJ, Brasch J, Goodman KM, Hansen L, Shapiro L, Honig B, Vakhrushev SY, Clausen H, Halim A., Proc. Natl. Acad. Sci. U.S.A. 114(42), 2017
PMID: 28973932
Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2.
Larsen ISB, Narimatsu Y, Joshi HJ, Yang Z, Harrison OJ, Brasch J, Shapiro L, Honig B, Vakhrushev SY, Clausen H, Halim A., J. Biol. Chem. 292(27), 2017
PMID: 28512129
O-mannosylation and N-glycosylation: two coordinated mechanisms regulating the tumour suppressor functions of E-cadherin in cancer.
Carvalho S, Oliveira T, Bartels MF, Miyoshi E, Pierce M, Taniguchi N, Carneiro F, Seruca R, Reis CA, Strahl S, Pinho SS., Oncotarget 7(40), 2016
PMID: 27533452
O-mannosylation of cadherins.
Baenziger JU., Proc. Natl. Acad. Sci. U.S.A. 110(52), 2013
PMID: 24344310
Protein O-mannosylation is crucial for E-cadherin-mediated cell adhesion.
Lommel M, Winterhalter PR, Willer T, Dahlhoff M, Schneider MR, Bartels MF, Renner-Muller I, Ruppert T, Wolf E, Strahl S., Proc. Natl. Acad. Sci. U.S.A. 110(52), 2013
PMID: 24297939
Molecular characterization of the human Calpha-formylglycine-generating enzyme.
Preusser-Kunze A, Mariappan M, Schmidt B, Gande SL, Mutenda K, Wenzel D, von Figura K, Dierks T., J. Biol. Chem. 280(15), 2005
PMID: 15657036
Mutant desmocollin-2 causes arrhythmogenic right ventricular cardiomyopathy.
Heuser A, Plovie ER, Ellinor PT, Grossmann KS, Shin JT, Wichter T, Basson CT, Lerman BB, Sasse-Klaassen S, Thierfelder L, MacRae CA, Gerull B., Am. J. Hum. Genet. 79(6), 2006
PMID: 17186466
An autosomal recessive mutation of DSG4 causes monilethrix through the ER stress response.
Kato M, Shimizu A, Yokoyama Y, Kaira K, Shimomura Y, Ishida-Yamamoto A, Kamei K, Tokunaga F, Ishikawa O., J. Invest. Dermatol. 135(5), 2015
PMID: 25615553
Desmosomes: regulators of cellular signaling and adhesion in epidermal health and disease.
Johnson JL, Najor NA, Green KJ., Cold Spring Harb Perspect Med 4(11), 2014
PMID: 25368015
Human derived cardiomyocytes: A decade of knowledge after the discovery of induced pluripotent stem cells.
Barbuti A, Benzoni P, Campostrini G, Dell'Era P., Dev. Dyn. 245(12), 2016
PMID: 27599668
In vitro functional analyses of arrhythmogenic right ventricular cardiomyopathy-associated desmoglein-2-missense variations.
Gaertner A, Klauke B, Stork I, Niehaus K, Niemann G, Gummert J, Milting H., PLoS ONE 7(10), 2012
PMID: 23071725
Mechanistic insights into arrhythmogenic right ventricular cardiomyopathy caused by desmocollin-2 mutations.
Gehmlich K, Syrris P, Peskett E, Evans A, Ehler E, Asimaki A, Anastasakis A, Tsatsopoulou A, Vouliotis AI, Stefanadis C, Saffitz JE, Protonotarios N, McKenna WJ., Cardiovasc. Res. 90(1), 2010
PMID: 21062920
Homozygous founder mutation in desmocollin-2 (DSC2) causes arrhythmogenic cardiomyopathy in the Hutterite population.
Gerull B, Kirchner F, Chong JX, Tagoe J, Chandrasekharan K, Strohm O, Waggoner D, Ober C, Duff HJ., Circ Cardiovasc Genet 6(4), 2013
PMID: 23863954
A novel desmocollin-2 mutation reveals insights into the molecular link between desmosomes and gap junctions.
Gehmlich K, Lambiase PD, Asimaki A, Ciaccio EJ, Ehler E, Syrris P, Saffitz JE, McKenna WJ., Heart Rhythm 8(5), 2011
PMID: 21220045
Functional assessment of potential splice site variants in arrhythmogenic right ventricular dysplasia/cardiomyopathy.
Groeneweg JA, Ummels A, Mulder M, Bikker H, van der Smagt JJ, van Mil AM, Homfray T, Post JG, Elvan A, van der Heijden JF, Houweling AC, Jongbloed JD, Wilde AA, van Tintelen JP, Hauer RN, Dooijes D., Heart Rhythm 11(11), 2014
PMID: 25087486
A genetic variants database for arrhythmogenic right ventricular dysplasia/cardiomyopathy.
van der Zwaag PA, Jongbloed JD, van den Berg MP, van der Smagt JJ, Jongbloed R, Bikker H, Hofstra RM, van Tintelen JP., Hum. Mutat. 30(9), 2009
PMID: 19569224
Transgenic mice overexpressing desmocollin-2 (DSC2) develop cardiomyopathy associated with myocardial inflammation and fibrotic remodeling.
Brodehl A, Belke DD, Garnett L, Martens K, Abdelfatah N, Rodriguez M, Diao C, Chen YX, Gordon PM, Nygren A, Gerull B., PLoS ONE 12(3), 2017
PMID: 28339476
Role of genetic testing in arrhythmogenic right ventricular cardiomyopathy/dysplasia.
Barahona-Dussault C, Benito B, Campuzano O, Iglesias A, Leung TL, Robb L, Talajic M, Brugada R., Clin. Genet. 77(1), 2009
PMID: 19863551
Analysis of protein-coding genetic variation in 60,706 humans.
Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG; Exome Aggregation Consortium, Lek M, Karczewski KJ, Minikel EV, Samocha KE, Banks E, Fennell T, O'Donnell-Luria AH, Ware JS, Hill AJ, Cummings BB, Tukiainen T, Birnbaum DP, Kosmicki JA, Duncan LE, Estrada K, Zhao F, Zou J, Pierce-Hoffman E, Berghout J, Cooper DN, Deflaux N, DePristo M, Do R, Flannick J, Fromer M, Gauthier L, Goldstein J, Gupta N, Howrigan D, Kiezun A, Kurki MI, Moonshine AL, Natarajan P, Orozco L, Peloso GM, Poplin R, Rivas MA, Ruano-Rubio V, Rose SA, Ruderfer DM, Shakir K, Stenson PD, Stevens C, Thomas BP, Tiao G, Tusie-Luna MT, Weisburd B, Won HH, Yu D, Altshuler DM, Ardissino D, Boehnke M, Danesh J, Donnelly S, Elosua R, Florez JC, Gabriel SB, Getz G, Glatt SJ, Hultman CM, Kathiresan S, Laakso M, McCarroll S, McCarthy MI, McGovern D, McPherson R, Neale BM, Palotie A, Purcell SM, Saleheen D, Scharf JM, Sklar P, Sullivan PF, Tuomilehto J, Tsuang MT, Watkins HC, Wilson JG, Daly MJ, MacArthur DG, Abboud HE, Abecasis G, Aguilar-Salinas CA, Arellano-Campos O, Atzmon G, Aukrust I, Barr CL, Bell GI, Bell GI, Bergen S, Bjorkhaug L, Blangero J, Bowden DW, Budman CL, Burtt NP, Centeno-Cruz F, Chambers JC, Chambert K, Clarke R, Collins R, Coppola G, Cordova EJ, Cortes ML, Cox NJ, Duggirala R, Farrall M, Fernandez-Lopez JC, Fontanillas P, Frayling TM, Freimer NB, Fuchsberger C, Garcia-Ortiz H, Goel A, Gomez-Vazquez MJ, Gonzalez-Villalpando ME, Gonzalez-Villalpando C, Grados MA, Groop L, Haiman CA, Hanis CL, Hanis CL, Hattersley AT, Henderson BE, Hopewell JC, Huerta-Chagoya A, Islas-Andrade S, Jacobs SB, Jalilzadeh S, Jenkinson CP, Moran J, Jimenez-Morale S, Kahler A, King RA, Kirov G, Kooner JS, Kyriakou T, Lee JY, Lehman DM, Lyon G, MacMahon W, Magnusson PK, Mahajan A, Marrugat J, Martinez-Hernandez A, Mathews CA, McVean G, Meigs JB, Meitinger T, Mendoza-Caamal E, Mercader JM, Mohlke KL, Moreno-Macias H, Morris AP, Najmi LA, Njolstad PR, O'Donovan MC, Ordonez-Sanchez ML, Owen MJ, Park T, Pauls DL, Posthuma D, Revilla-Monsalve C, Riba L, Ripke S, Rodriguez-Guillen R, Rodriguez-Torres M, Sandor P, Seielstad M, Sladek R, Soberon X, Spector TD, Tai SE, Teslovich TM, Walford G, Wilkens LR, Williams AL., Nature 536(7616), 2016
PMID: 27535533
Export

Markieren/ Markierung löschen
Markierte Publikationen

Open Data PUB

Web of Science

Dieser Datensatz im Web of Science®
Quellen

PMID: 30942563
PubMed | Europe PMC

Suchen in

Google Scholar