Intrinsic lipid binding activity of ATG16L1 is essential for membrane anchoring and autophagy.

EMBO J. (in press)
Dudley, L.J., Gonzales-Cabodevilla, A. Makar, A.N., Sztacho, M., Marsh, J., Houston, D.R. Martens, S., Jiang, X. and Gammoh, N.

Molecular Cell (2019).
Turco, E., Witt, M., Abert, C., Bock-Bierbaum, T., Su, M.Y., Trapannone, R., Sztacho, M., Danieli, A., Shi, X., Zaffagnini, G., Gamper, A., Schuschnig, M., Fracchiolla, D., Bernklau, D., Romanov, J., Hartl, M., Hurley, J.H., Daumke, O., and Martens, S.

In this manuscript we show that the C-terminal domain of FIP200 binds to the p62 cargo receptor promoting the recruitment and activation of the autophagy machinery at ubiquitin condensates. This in turn results in their sequestration within autophagosomes and eventually degradation of the condensates. Structural studies showed that the C-terminal domain of FIP200 is shaped like a claw.  

In Autophagy: Methods and Protocols, N. Ktistakis, and O. Florey, eds. (New York, NY, Springer New York), pp. 189-196. (2019).
Abert, C., and Martens, S.

Science Signaling 11 (2018).
Martens, S.

Autophagy. (2018).
Zaffagnini, G., Savova, A., Danieli, A., Romanov, J., Tremel, S., Ebner, M., Peterbauer, T., Sztacho, M., Trapannone, R., Tarafder, A.K., Sachse, C., and Martens, S.

The EMBO Journal (2018).
Fracchiolla, D., Martens S.

The EMBO Journal (2018).  
Zaffagnini, G., Savova, A., Danieli, A., Romanov, J., Tremel, S., Ebner, M., Peterbauer, T., Sztacho, M., Trapannone, R., Tarafder, A.K., Sachse, C., and Martens, S.

In this paper, we show that in vitro the autophagy receptor p62 and ubiquitinated substrates spontaneously phase separate into clusters. Mechanistically, this is based on the crosslinking of p62 filaments by the substrates. The cargo receptor NBR1 directly stimulates this process. We further uncover multiple modes of regulation of the clustering reaction that suggest how this process can be integrated into general proteostasis and coordinated with autophagosome formation.

Nat Comms (2017). 
Sánchez-Wandelmer, J., Rohringer, S., Schuschnig, M., Zens, B., Abreu, S., Gao, J., Ungermann, C., Martens, S., Kraft, C., and Reggiori, F.

The EMBO Journal (2017). 
Galluzzi, L., … Martens, S., et al.

EMBO reports, (2017).
Abreu, S., Kriegenburg, F., Gomez-Sanchez, R., Mari, M., Sanchez-Wandelmer, J., Skytte Rasmussen, M., Soares Guimaraes, R., Zens, B., Schuschnig, M., Hardenberg, R., Peter, M., Johansen, T., Kraft. C., Martens, S., Reggiori, F. 

Autophagy, (2017).
Fracchiolla, D., Sawa-Makarska, J., and Martens, S.

In this commentary to the eLife paper below we discuss the dual roles of LIR motifs in autophagy. In particular, we speculate that LIR motifs may also be involved in the recruitment of the autophagy machinery to the cargo. Thus these motifs may have roles upstream of Atg8 protein binding. The picture on the right was hand drawn by Dorotea.

eLife 5, e18544. (2016).
Fracchiolla, D., Sawa-Makarska, J., Zens, B., de Ruiter, A., Zaffagnini, G., Brezovich, A., Romanov, J., Runggatscher, K., Kraft, C., Zagrovic, B., and Martens, S.

In this paper we show that the yeast cargo receptor Atg19 directly interacts with the E3-like Atg12–Atg5-Atg16 complex via its LIR motifs. The receptor thereby recruits the E3 to prApe1 to locally stimulate Atg8 conjugation to phosphatidylethanolamine (PE) in the membrane. In a fully reconstituted system we show that these interactions are sufficient to mediate Atg8 conjugation at the cargo. The recruitment of the E3-like Atg12–Atg5-Atg16 complex to cargo material may be a conserved mechanism since we show that also human cargo receptors bind the ATG5 protein.

Methods in Enzymology (2016).
Fracchiolla, D., B. Zens, and S. Martens


Journal of Molecular Biology. (2016).
Martens, S., Nakamura, S., and Yoshimori, T.

Journal of Structural Biology. (2016).
Turco, E., and Martens, S.

Trends in Cell Biology (2016).
Martens, S.

Proceedings of the National Academy of Sciences. (2016).
Richter, B., Sliter, D.A., Herhaus, L., Stolz, A., Wang, C., Beli, P., Zaffagnini, G., Wild, P., Martens, S., Wagner, S.A., Youle, R.J., and Dikic, I.

J Mol Biol, 10.1016/j.jmb.2016.02.004 (2016).
Zaffagnini G, Martens S

eLife 2015;10.7554/eLife.08941 (2015).
Wurzer B, Zaffagnini G, Fracchiolla D, Turco E, Abert C, Romanov J, Martens S

Using fluorescently labeled proteins combined with imaging-based techniques we show that the human autophagic cargo receptor p62/SQSTM-1 employs oligomerization to accumulate at ubiquitin-covered cargo material. In vivo this activity is required for p62 to localize to intracellular Salmonella. At the same time oligomerization mediates avid binding to the autophagosomal membrane via its interaction with ATG8-family proteins.  We further show in a reconstituted system that p62 is able to mediate membrane bending around cargo material.

NAT CELL BIOL; 17(7):841-2.(2015).
Martens S, Bachmair A.

Methods 75:37-43. March 2015.
Zens B, Sawa-Makarska J, Martens S

Cell Cycle. 13(15):2313-4.(2014).
Sawa-Makarska J, Martens S.

EMBO Rep. 15(8):862-70.(2014).
Pfaffenwimmer T, Reiter W, Brach T, Nogellova V, Papinski D, Schuschnig M, Abert C, Ammerer G, Martens S, Kraft C.

NAT CELL BIOL;5(16):425-33.(2014).
Sawa-Makarska, Justyna; Abert, Christine; Romanov, Julia; Zens, Bettina; Ibiricu, Iosune; Martens, Sascha.

In this paper we show that the Atg19 cargo receptor contains multiple interaction sites for the Atg8 protein in its C-terminus. Atg8 proteins decorate the autophagosomal membrane and collectively these multiple interaction sites for Atg8 mediate the bending of the membrane around autophagic cargo material. In vivo the close apposition of the autophagosomal membrane and the cargo will exclude non-cargo material from its delivery into the lysosomal system.

See also comments in Current Biology and Nature Cell Biology:
Autophagy: close contact keeps out the uninvited.
Selective autophagy goes exclusive.

Autophagy. 9(9):1286-91.(2013).
Martens S, Rusten TE, Kraft C.

EMBO J;31(22):4304-17. (2012).
Romanov, Julia; Walczak, Marta; Ibiricu, Iosune; Schüchner, Stefan; Ogris, Egon; Kraft, Claudine; Martens, Sascha.

In this paper we show how the conserved Atg5-Atg12/Atg16 complex binds to membranes and how this is regulated. In addition we elucidate the function of membrane binding by this complex during autophagosome formation. In particular we find that the membrane binding by the Atg5-Atg12/Atg16 complex is required for membrane tethering and Atg8 conjugation to the membrane lipid phosphatidylethanolamine. This is the first paper describing the reconstitution of autophagic processes using giant unilamellar vesicles.

CURR OPIN CELL BIOL;24(4):496-501. (2012).
Kraft,C., Martens, S.

Curr Top Membr. 68:141-59.(2011).
Martens S, McMahon HT.

Proc Natl Acad Sci U S A.108(23):9431-6.(2011).
Richmond DL, Schmid EM, Martens S, Stachowiak JC, Liska N, Fletcher DA.

BMC Biol. Jan 28;9:7.(2011).
Pawlowski N, Khaminets A, Hunn JP, Papic N, Schmidt A, Uthaiah RC, Lange R, Vopper G, Martens S, Wolf E, Howard JC.

Cell. 140(5):601-5.(2010).
McMahon HT, Kozlov MM, Martens S.

Science. 327(5973):1614-8.(2010).
Groffen AJ, Martens S, Díez Arazola R, Cornelisse LN, Lozovaya N, de Jong AP, Goriounova NA, Habets RL, Takai Y, Borst JG, Brose N, McMahon HT, Verhage M.

Biochem Soc Trans. 38(Pt 1):213-6.(2010).
Martens S.

PLoS One. 5(1):e8648 (2010).
Zhao YO, Könen-Waisman S, Taylor GA, Martens S, Howard JC.

Nat Chem Biol. 6(1):46-53.(2010).
Gerlach H, Laumann V, Martens S, Becker CF, Goody RS, Geyer M.

Mol Biol Cell. 19(12):5093-103.(2008).
Lynch KL, Gerona RR, Kielar DM, Martens S, McMahon HT, Martin TF.

EMBO J. 27(19):2495-509.(2008).
Hunn JP, Koenen-Waisman S, Papic N, Schroeder N, Pawlowski N, Lange R, Kaiser F, Zerrahn J, Martens S, Howard JC.

Nat Rev Mol Cell Biol. 9(7):543-56.(2008).
Martens S, McMahon HT.

Nature. 449(7164):923-7.(2007).
Daumke O, Lundmark R, Vallis Y, Martens S, Butler PJ, McMahon HT.

Science. 316(5828):1205-8.(2007).
Martens S, Kozlov MM, McMahon HT.

Annu Rev Cell Dev Biol. 22:559-89.(2006).
Martens S, Howard J.

PLoS Pathog. 1(3):e24.(2005).
Martens S, Parvanova I, Zerrahn J, Griffiths G, Schell G, Reichmann G, Howard JC.

Genome Biol. 3(8):REPORTS4025. (2002).
Martens S.

Prof. Sascha 
Dr.Bohr-Gasse 9, 1030 Vienna, Austria | Room: 5.113

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