The Stasyk Laboratory: Molecular architecture of native lysosomal protein assemblies
Lysosomes are intracellular signaling platforms that govern cell growth, division and differentiation. Although our knowledge of the molecular mechanisms of the sensing of essential nutrients has advanced significantly, we still lack information on the interplay between the numerous components of sensing and signaling machineries. The LAMTOR/Ragulator complex is a crucial regulator of lysosomal mTORC1, MAPK and AMPK signaling. Via the BORC complex, LAMTOR also coordinates lysosome biogenesis. The existence of distinct LAMTOR complexes on lysosomes raises questions on how anabolic and catabolic signaling, lysosomal biogenesis and positioning are coordinated.
We are aiming to identify all LAMTOR- and BORC-associated protein assemblies on intact lysosomes and to obtain evidence for direct and endogenous protein-protein interactions. We are applying cross-linking mass spectrometry (XL-MS) in combination with subcellular fractionation to understand the molecular architectures of the protein complexes under different physiological conditions. Our approach captures native endogenous protein interactions using a chemical cross-linker that is reactive towards specific amino-acid side chains that are in close spatial proximity.
Publications
- BORC assemblies integrate BLOC-1 subunits to diversify endosomal trafficking functions. de Araujo MEG*, J Amann S*, Stasyk T*, Schleiffer A, Rauch E, Flümann P, Singer II, Kremser L, Dostal V, Laopanupong T, Obojes N, Wallnöfer MH, Gradl FS, Kurzbauer R, Krebiehl C, Kofler S, Grishkovskaya I, Vogel GF, Hess MW, Sarg B, Clausen T, Haselbach D, Huber LA. Proc Natl Acad Sci U S A. 2026 Jan 27;123(4):e2515691123. doi: 10.1073/pnas.2515691123.
- LAMTOR/Ragulator regulates lipid metabolism in macrophages and foam cell differentiation. Lamberti G, De Smet CH, Angelova M, Kremser L, Taub N, Herrmann C, Hess MW, Rainer J, Tancevski I, Schweigreiter R, Kofler R, Schmiedinger T, Vietor I, Trajanoski Z, Ejsing CS, Lindner HH, Huber L, Stasyk T. FEBS Lett. 2020; 594(1):31-42. doi: 10.1002/1873-3468.13579
- Biogenesis of lysosome-related organelles complex-1 (BORC) regulates late endosomal/lysosomal size through PIKfyve-dependent phosphatidylinositol-3,5-bisphosphate. Yordanov TE, Hipolito VEB, Liebscher G, Vogel GF, Stasyk T, Herrmann C, Geley S, Teis D, Botelho RJ, Hess MW, Huber LA. Traffic. 2019; 20(9):674-696. doi: 10.1111/tra.12679
- LAMTOR/Ragulator is a negative regulator of Arl8b- and BORC-dependent late endosomal positioning. Filipek PA, de Araujo MEG, Vogel GF, De Smet CH, Eberharter D, Rebsamen M, Rudashevskaya EL, Kremser L, Yordanov T, Tschaikner P, Fürnrohr BG, Lechner S, Dunzendorfer-Matt T, Scheffzek K, Bennett KL, Superti-Furga G, Lindner HH, Stasyk T*, Huber LA*. J Cell Biol. 2017; 216(12):4199-4215. doi: 10.1083/jcb.201703061, *equal contribution as corresponding authors
- Crystal structure of the human lysosomal mTORC1 scaffold complex and its impact on signaling. de Araujo MEG, Naschberger A, Fürnrohr BG, Stasyk T, Dunzendorfer-Matt T, Lechner S, Welti S, Kremser L, Shivalingaiah G, Offterdinger M, Lindner HH, Huber LA, Scheffzek K. Science. 2017 20;358(6361):377-381. doi: 10.1126/science.aao1583
- SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Rebsamen M, Pochini L, Stasyk T, de Araújo ME, Galluccio M, Kandasamy RK, Snijder B, Fauster A, Rudashevskaya EL, Bruckner M, Scorzoni S, Filipek PA, Huber KV, Bigenzahn JW, Heinz LX, Kraft C, Bennett KL, Indiveri C, Huber LA, Superti-Furga G. Nature. 2015, 519(7544):477-8,1 doi: 10.1038/nature14107
Funding
- FWF P36975
Team and Contact
Dr. Taras Stasyk
Email: taras.stasyk@i-med.ac.at
Phone: +43512900370340
Name
Taras Stasyk
Eva Rauch
Martina Höllwarth
Position
Group leader
PhD student
PhD student
