A03

Ykt6-dependent trafficking of Wnts

Funding period: 2017-2021

Project A03 ended

Project Leaders

Prof. Dr. Julia Gross

Prof. Dr. Julia Gross

 Project Leader A03

Abstract

Exosomal Wnt secretion via multivesicular bodies (MVBs) depends on the unusual v-SNARE Ykt6. In the proposed project, we will analyze Ykt6-dependent trafficking dynamics of Wnt3A into MVBs biochemically and by microscopy. To investigate the Ykt6-mediated sorting mechanism of exosomal Wnt3A we will characterize binding of different Ykt6 mutants and Evi deletion constructs and identify new factors involved in the Ykt6-mediated sorting by a proteomics approach. Further characterization of these factors in cell culture will be complemented with an in vivo study of Ykt6 and new interactors in Drosophila melanogaster.

Project-related Publications

Wnt10b GSK3β dependent Wnt/STOP signaling prevents aneuploidy in human somatic cells

Lin YC, Haas A, Bufe A, Parbin S, Hennecke M, Voloshanenko O, Gross J, Boutros M, Acebron SP, Bastians H. Life Sci Alliance. 2020 Nov 30;4(1):e202000855. Print 2021 Jan.
PMID: 33257473

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Phosphorylation of Ykt6 SNARE Domain Regulates Its Membrane Recruitment and Activity

Karuna M P, Witte L, Linnemannstoens K, Choezom D, Danieli-Mackay A, Honemann-Capito M, Gross JC. Biomolecules. 2020 Nov 16;10(11):E1560.

PMID: 33207719

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The kinesin motor Klp98A mediates apical to basal Wg transport

Witte L, Linnemannstöns K, Schmidt K, Honemann-Capito M, Grawe F, Wodarz A, Gross JC. Development. 2020 Aug 14;147(15):dev186833. doi: 10.1242/dev.186833.
PMID: 32665246

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Ykt6-dependent endosomal recycling is required for Wnt secretion in the Drosophila wing epithelium

Linnemannstöns K, Witte L, Karuna P, Kittel J, Danieli A, Müller D, Nitsch L, Honemann-Capito M, Grawe F, Wodarz A, Gross JC. Development. 2020 Aug 14;147(15):dev185421. PMID: 32611603

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eGFP-tagged Wnt-3a enables functional analysis of Wnt trafficking and signaling and kinetic assessment of Wnt binding to full-length Frizzled

Wesslowski J, Kozielewicz P, Wang X, Cui H, Schihada H, Kranz D, Karuna M P, Levkin P, Gross JC, Boutros M, Schulte G, Davidson G. J Biol Chem. 2020 May 7. pii: jbc.RA120.012892. PMID:32381507

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The Mingle-Mangle of Wnt Signaling and Extracellular Vesicles: Functional Implications for Heart Research

Gross JC, Zelarayán LC. Front Cardiovasc Med. 2018 Feb 22;5:10. PMID:29564334

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Neutral sphingomyelinases control extracellular vesicles budding from the plasma membrane

Menck K, Sönmezer C, Worst TS, Schulz M, Dihazi GH, Streit F, Erdmann G, Kling S, Boutros M, Binder C, Gross JC. J Extracell Vesicles. 2017 Sep 26;6(1):1378056. doi: 10.1080/20013078.2017.1378056. eCollection 2017. PMID: 29184623

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Biochemical Methods to Analyze Wnt Protein Secretion

Glaeser K, Boutros M, Gross JC. Methods Mol Biol. 2016;1481:17-28. doi: 10.1007/978-1-4939-6393-5_3. PMID: 27590148

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Molecular dissection of Wnt3a-Frizzled8 interaction reveals essential and modulatory determinants of Wnt signaling activity

Kumar S, Žigman M, Patel TR, Trageser B, Gross JC, Rahm K, Boutros M, Gradl D, Steinbeisser H, Holstein T, Stetefeld J, Özbek S. BMC Biol. 2014 May 30;12:44. doi: 10.1186/1741-7007-12-44. PMID: 24885675

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Active Wnt proteins are secreted on exosomes

Gross JC, Chaudhary V, Bartscherer K, Boutros M. Nat Cell Biol. 2012 Oct;14(10):1036-45. doi: 10.1038/ncb2574. Epub 2012 Sep 16. PMID: 22983114

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