Groupleader: Thomas Söllner
Thomas Söllner
Regulated Membrane Fusion: Molecular Mechanisms and Machinery
Research
Our research aims to reveal the mechanisms and machinery underlying intracellular vesicle targeting and regulated membrane fusion. Regulated exocytosis plays a key role in short- and long-range communication and allows complex organisms to react appropriately to various stimuli by releasing mediators, such as hormones, growth factors, and neurotransmitters in a temporally and spatially controlled manner.
We are taking 2 avenues to accomplish our research goals. One is intended to isolate new components, followed by a functional analysis in an environment close to intact cells. The other shall reveal the detailed molecular mechanisms of how distinct components fulfill their functions by making use of a completely reconstituted assay employing SNARE-mediated fusion as an analysis platform. The primary model system for all of these studies is the neuronal synapse, which (like other membrane fusion) steps employs a basic targeting and fusion machinery, but in addition is characterized by its localized vesicle docking and precise regulation. The long-term goal is to reconstitute the sequential series of molecular events, starting with synaptic vesicle recruitment and docking to the active zone, followed by various steps priming the machinery and finally resulting in Ca2+ triggered fusion.
To explore the exact molecular mechanisms by which individual components or functional protein assemblies regulate vesicle fusion, we make use of our previous observation that SNAREs are the minimal machinery for membrane fusion. SNARE proteins, a family of compartmentally specific integral membrane proteins, spontaneously fuse lipid bilayers when reconstituted into liposomes. Addition of regulatory components will affect the fusion kinetics and probability. Basic machinery presently under analysis includes tethering proteins, Rab proteins and their effectors, Sec1/Munc18 proteins, and calcium-sensors. The potentially superimposed fine-tuning underlying synapse modulation during adaptive processes, such as synaptic facilitation and repression, will become another subject of investigation.
Download BZH Report Söllner 2014-2016
Lab Members
PhD student
Lab:Room 223
/ Phone: +49 6221 54-4735
Mail:timon.andre@bzh.uni-heidelberg.de
TA
Lab:Room 221
/ Phone: +49 6221 54-5343
Mail:lara.braun@bzh.uni-heidelberg.de
PhD student
Lab:Room 222
/ Phone: +49 6221 54-5344
Mail:philipp.brenner@bzh.uni-heidelberg.de
scientific staff
Lab:Room 222
/ Phone: +49 6221 54-5344
Mail:eda.demirel@bzh.uni-heidelberg.de
secretary
Office:Room 205
/ Phone: +49 6221 54-5340
Mail:martina.franke@bzh.uni-heidelberg.de
Sekr. Söllner 2.OG: 6:45 - 11:00 Uhr
Sekr. Brunner 5. OG: 11:00 - 14:30 Uhr
Sekr. Söllner 2.OG: 14:30 - 15:15 Uhr
TA
Lab:Room 221
/ Phone: +49 6221 54-5343
Mail:uschi.goebel@bzh.uni-heidelberg.de
staff scientist
Lab:Room 221
/ Phone: +49 6221 54-5343
Office:Room 201
/ Phone: +49 6221 54-5345
Mail:joerg.malsam@bzh.uni-heidelberg.de
PhD student
Lab:Room 221
/ Phone: +49 6221 54-5343
Mail:jacqueline.murach@bzh.uni-heidelberg.de
postdoc
Lab:Room 222
/ Phone: +49 6221 54-5344
Mail:kerstin.rink@bzh.uni-heidelberg.de
TA
Lab:Room 221
/ Phone: +49 6221 54-5343
Mail:andrea.scheutzow@bzh.uni-heidelberg.de
CV
| 1980 - 1981 | Study of biology at the University of Regensburg |
| 1982 - 1986 | Study of biology at the Ludwig-Maximilians University Munich |
| 1987 - 1991 |
Ph.D. student at the Ludwig-Maximilians University Munich (laboratory of Prof. Dr. Dr. Walter Neupert) |
| 1991 – 1993 |
Post-doctoral fellow at Sloan-Kettering Institute, New York, USA (laboratory of Prof. Dr. James E. Rothman) |
| 1994 - 1997 |
Assistant Laboratory Member at Sloan-Kettering Institute, New York, USA (laboratory of Prof. Dr. James E. Rothman) |
| 1998 - 2004 |
Assistant Member (Assistant Professor) at Sloan-Kettering Institute, New York, USA |
| 2004 - 2005 |
Associate Member (Associate Professor) at Sloan-Kettering Institute, New York, USA |
| since 15.09.2005 |
Professor at the University of Heidelberg (BZH) |
| 2016 - 2018 | Director of the Heidelberg University Biochemistry Center (BZH) |
Publications
2020
André T, Classen J, Brenner P, Betts MJ, Dörr B, Kreye S, Zuidinga B, Meijer M, Russell RB, Verhage M, Söllner TH (2020). The Interaction of Munc18-1 Helix 11 and 12 with the Central Region of the VAMP2 SNARE Motif Is Essential for SNARE Templating and Synaptic Transmission. eNeuro 7, https://doi.org/10.1523/ENEURO.0278-20.2020
Malsam J, Bärfuss S, Trimbuch Th, Zarebidaki F, Sonnen A, Wild K, Scheutzow A, Rohland L, Mayer M, Sinning I, Briggs J, Rosenmund Ch, Söllner TH (2020) Complexin Surpresses Spontaneous Exocytosis by Capturing the Membrane-Proximal Regions of VAMP2 and SNAP25. Cell Reports 32, 107926 July 21, https://doi.org/10.1016/j.celrep.2020.107926
Ginger L, Malsam M, Sonnen A, Morado D, Scheutzow A, Söllner TH, Briggs J (2020) Arrangements of proteins at reconstituted synaptic vesicle fusion sites depend on membrane separation. FEBS Letters, https://doi.org/10.1002/1873-3468.13916
2019
Ruiter M, Kádková A, Scheutzow A, Malsam J, Söllner TH, Sørensen JB (2019) An Electrostatic Energy Barrier for SNARE-Dependent Spontaneous and Evoked Synaptic Transmission. Cell Rep. 2019 Feb 26;26(9):2340-2352.e5. doi: 10.1016/j.celrep.2019.01.103.
Brose N, Brunger A, Cafiso D, Chapman ER, Diao J, Hughson FM, Jackson MB, Jahn R, Lindau M, Ma C, Rizo J, Shin YK, Söllner TH, Tamm L, Yoon TY, Zhang Y (2019) Synaptic vesicle fusion: today and beyond Nat Struct Mol Biol. Aug;26(8):663-668. doi: 10.1038/s41594-019-0277-z.
2018
Söllner, T. Malsam, J. (2018) Uncovering the “secret” Lives of Vacuolar Fusion pores in living cells. EMBOJ 37 (19) DOI:10.15252/embj.2018100656.
Meijer M., Dörr B., Lammertse H., Blithikioti C., van Weering J., Toonen R., Söllner T.H., Verhage M. (2018) Tyrosine phosphorylation of Munc18-1 inhibits synaptic transmission by preventin SNARE assembly.
The EMBO Journal 37(2): 300-320
2017
Weber P., Batoulis H., Rink K.M., Dahlhoff S., Pinkwart K., Söllner T.H., Lang T. (2017) Electrostatic anchoring precedes stable membrane attachment of SNAP25/SNAP23 to the plasma membrane.
eLife 6:e19394. DOI: 10.7554/eLife.19394
2016
Schupp M, Malsam J, Ruiter M, Scheutzow A, Wierda KD, Söllner TH, Sørensen JB.
Interactions Between SNAP-25 and Synaptotagmin-1 Are Involved in Vesicle Priming, Clamping Spontaneous and Stimulating Evoked Neurotransmission.
J Neurosci. 2016; 36(47):11865-11880
Munch, A.S., Kedar, G.H., van Weering, J.R.T., Vazquez-Sanchez, S., He, E., Andre, T., Braun, T., Söllner, T.H., Verhage, M., Sørensen, J.B. (2016) Extension of Helix 12 in Munc18-1 Induces Vesicle Priming. J. Neurosci. 36(26): 6881-6891.
2015
Kedar, G.H., Munch, A.S., van Weering, J.R.T., Malsam, J., Scheutzow, A., de Wit, H., Houy, S., Tawfik, B., Söllner, T.H., Sørensen, J.B., Verhage, M. (2015) A post-docking role of synaptotagmin 1-C2B domain bottom residues R398/399 in mouse chromaffin cells. J. Neurosci. 35(42): 14172-14182.
2014
Parisotto, D., Pfau, M., Scheutzow, A., Wild, K., Mayer, M.P., Malsam, J., Sinning, I., Söllner, T.H. (2014) An Extended Helical Conformation in Domain 3a of Munc18-1 Provides a Template for SNARE (Soluble N-Ethylmaleimide-sensitive Factor Attchment Protein Receptor) Complex Assembly. J.Biol.Chem. 289, 9639-9650.
Bharat, T.A., Malsam, J., Hagen, W.J., Scheutzow, A., Söllner, T.H., Briggs, J.A. (2014) SNARE and regulatory proteins induce local membrane protrusions to prime docked vesicles for fast calsium-triggered fusion. EMBO reports 15:3, 308-314.
2012
Malsam, J., Parisotto, D., Bharat, T.A., Scheutzow A., Krause, J.M., Briggs, J.A., Söllner, T.H. (2012) Complexin arrests a pool of docked vesicles for fast Ca (2+)-dependent release. EMBO J. 31, 3270-3281
Parisotto, D., Malsam, J., Scheutzow, A., Krause, J.M., Söllner, T.H. (2012) SNAREpin Assembly by Munc18-1 Requires Previous Vesicle Docking by Synaptotagmin 1. J. Biol. Chem. 287, 31041-31049
2011
Schollmeier, Y., Krause, J. M., Kreye, S., Malsam, J., Söllner, T.H. (2011). Resolving the Function of Distinct Munc18-1/SNARE Protein Interaction Modes in a Reconstituted Membrane Fusion. JBC 286 No. 35, 30582-30590.
Malsam, J., and Söllner, T.H. (2011). Organization of SNAREs within the Golgi stack. in ‘The Golgi’, Coldspring Harbor Perspectives in Biology (editors Warren, G. and Rothman, J.) Cold Spring Harbor Laboratory Press
2010
Kögel, T., Rudolf, R., Hodneland, E., Hellwig, A., Kuznetsov, S., Seiler, F., Söllner, T.H., Barroso, J., Gerdes, H.-H. (2010). Distinct Roles of Myosin Va in Membrane Remodeling and Exocytosis of Secretory Granules. Traffic, 11: 637-650.
2009
Seiler, F., Malsam, J., Krause, JM., Söllner, T.H. (2009). A role of complexin-lipid interactions in membrane fusion. FEBS letters, 583: 2343-8.
Malsam, J., Seiler, F., Schollmeier, Y., Rusu, P., Krause, JM., Söllner, T.H. (2009). The carboxy-terminal domain of complexin I stimulates liposome fusion. Proc. Natl. Acad. Sci. USA, 106: 2001-2006.
2008
Malsam, J., Kreye, S., Söllner, T.H. (2008). Membrane fusion: SNAREs and regulation. Cell Mol. Life. Sci., 65: 2814-2832.
Kreye, S., Malsam, J., Söllner, T.H. (2008). In vitro assays to measure SNARE mediated membrane fusion. Methods in Mol. Biol. 440: 37-50.
2007
Moelleken, J., Malsam, J., Betts, M.J., Movafeghi, A., Reckmann, I., Meissner, I., Hellwig, A., Russell, R.B., Söllner, T.H., Brügger, B., Wieland, F.T. (2007). Differential localization of isoformic coatomer complexes within the Golgi apparatus. Proc. Natl. Acad. Sci. USA, 104: 4425-30.
Söllner, T.H. (2007). Membrane trafficking. FEBS Letters, 581: 2075.
Söllner, T.H. (2007). Lipid droplets highjack SNAREs. Nat. Cell Biol., 9:1219-20.
2005
Cosson, P., Ravazzola, M., Varlamov, O., Söllner, T.H., Di Liberto, M., Volchuk, A., Rothman J.E., Orci, L. (2005). Dynamic transport of SNARE proteins in the Golgi apparatus. Proc Natl Acad Sci U S A, 102:14647-52.
2004
Cheng, Y. Sequeira, S.M., Malinina, L., Tereshko, V., Söllner, T.H., and Patel, D.J. (2004). Crystallographic identification of Ca2+ and Sr2+ coordination sites in synaptotagmin I C2B domain. Protein Science, 13: 2665-2672.
Söllner, T.H. (2004) Intracellular and viral membrane fusion: a uniting mechanism. Curr. Opinion Cell Biol, 16: 429-435.
Fukasawa, M., Varlamov, O., Eng, W.S., Söllner, T.H., and Rothman, J.E. (2004). Localization and activity of the SNARE Ykt6 determined by its regulatory domain and palmitoylation. Proc. Natl. Acad. Sci. USA, 101: 4815-1820.
Varlamov, O., Volchuk, A., Rahimian, V., Doege, C.A. Paumet, F., Eng, W.S, Arango, N.C., Parlati, F., Ravazzola, M., Orci, L, Söllner, T.H., and Rothman, J.E. (2004). i-SNAREs, inhibitory SNAREs that fine-tune the specificity of membrane fusion. J. Cell Biol., 164: 79-88.
2003
Söllner, T.H., and Sequeira, S. (2003) S-nitrosylation of NSF controls membrane trafficking. Cell, 115: 127-129.
Burri, L., Varlamov, O., Doege, C., Hofman, K., Beilharz, T., Rothman, J.E., Söllner, T.H., and Lithgow, T. (2003). A SNARE required for retrograde transport to the endoplasmic reticulum. Proc. Natl. Acad. Sci. USA, 100: 9873-9877.
Hu, C., Ahmed, M., Melia, T.J., Söllner, T.H., Mayer, T., and Rothman, J.E. (2003). Fusion of cells by flipped SNAREs. Science, 300: 1745-1749.
Söllner T.H. (2003). Regulated exocytosis and SNARE function. Mol. Memb. Biol., 20: 209-220.
Mahal, L.K., Sequeira, S.M., Gureasko, J., and Söllner, T.H. (2002). Calcium-independent stimulation of membrane fusion and SNAREpin formation by synaptotagmin I. J.Cell Biol., 158: 273-282.
2002
Parlati, F., Varlamov, O., Paz, K., McNew, J.A., Hurtado, D., Söllner, T.H., and Rothman, J.E. (2002). Distinct SNARE complexes mediating membrane fusion in Golgi
transport based on combinatorial specificity. Proc. Natl. Acad. Sci. USA, 99: 5424-5429.
Melia, T.J., Weber, T., McNew, J.A., Fisher, L.E., Johnston, R.J., Parlati, F., Mahal, L.K. Söllner, T.H., and Rothman, J.E. (2002). Regulation of membrane fusion by the membrane-proximal coil of the t SNARE during zippering of SNAREpins. J. Cell Biol, 158: 929-940.
2000
McNew, J.A., Parlati, F., Fukuda, R., Johnston, R.J., Paz, K., Paumet, F., Söllner, T.H., and Rothman, J.E. (2000). Compartmental specificity of cellular membrane fusion encoded in SNARE proteins. Nature, 407: 153-159.
Parlati, F., McNew, J.E., Fukuda, R., Miller, R., Söllner, T.H., and Rothman, J.E. (2000). Topological restriction of SNARE-dependent membrane fusion. Nature, 407: 194-198.
Fukuda, R., McNew, J.A., Weber, T., Parlati, F., Engel, T., Nickel, W., Rothman, J.E., and Söllner, T.H. (2000) Functional architecture of an intracellular membrane t-SNARE. Nature, 407: 198-202.
Brügger, B., Nickel, W., Weber, T., Parlati, F., McNew, J.A., Rothman, J.E. and Söllner, T. (2000). Putative fusogenic activity of NSF is restricted to a lipid mixture whose coalescence is also triggered by other factors. EMBO J., 19: 1272-1278.
McNew, J.A., Weber, T., Parlati, F., Johnston, R., Melia, T.J., Söllner, T.H., and Rothman, J.E. (2000). Close is not enough: SNARE-dependent membrane fusion requires an active mechanism that transduces force to membrane anchors. J.Cell Biol., 150: 105-117.
Weber, T., Parlati, F., McNew, J.A., Johnston, R.J., Westermann, B., Söllner, T.H., and Rothman, J.E. (2000). SNAREpins are functionally resistant to disruption by NSF and aSNAP. J.Cell Biol., 149: 1063-1072.
1993-1998
Hohl., T.M., Parlati, F., Wimmer, C., Rothman, J.E., Söllner, T.H., and Engelhardt, H. (1998). Arrangement of subunits in 20 S particles consisting of NSF, SNAPs, and SNARE complexes. Mol. Cell, 2: 539-548.
Weber, T., Zemelman, B.V., McNew, J.A., Westermann, B., Gmachl, M., Parlati, F., Söllner, T.H., and Rothman, J.E. (1998). SNAREpins: minimal machinery for membrane fusion. Cell, 92: 759-772.
Rothman, J.E., and Söllner, T.H. (1997). Throttles and Dampers: controlling the engine of membrane fusion. Science, 276: 1212-1213.
Nagahama, M., Orci, L., Ravazzola, M., Amherdt, M., Lacomis, L., Tempst, P., Rothman, J.E., and Söllner, T.H. (1996). A v-SNARE implicated in intra-Golgi transport. J. Cell. Biol, 133: 507-516
Søgaard, M., Tani, K., Ye, R.R., Geromanos, S., Tempst, T., Kirchausen, T., Rothman, J.E., and Söllner, T. (1994). A rab protein is required for the assembly of SNARE complexes in the docking of transport vesicles. Cell, 78: 937-948.
Söllner, T., Bennett, M.K., Whiteheart, S.W., Scheller, R.H., and Rothman, J.E. (1993). A protein assembly - disassembly pathway that may correspond to sequential steps of synaptic vesicle docking, activation and fusion. Cell, 75: 409-418.
Söllner, T., Whiteheart, S.W., Brunner, M., Erdjument-Bromage, H., Geromanos, S., Tempst, P., and Rothman, J.E. (1993). SNAP receptors implicated in vesicle targeting and fusion. Nature, 362: 318-324.
Contact
Biochemistry Center (BZH)
Im Neuenheimer Feld 328
69120 Heidelberg
Secretary: Martina Franke
