The central goal of the Fakler lab is to investigate and understand

‘How rapid signal transduction at and across the plasma membrane is organized and operated’.

This signaling that is fundamental for perception, processing and storage of information is mediated by protein assemblies (or complexes) integral to the cell membrane and working as ion channels, transporters or receptors coupled to G-proteins and other transducers. It is our long-standing interest to get insight into

• How these complexes are assembled or what subunits are required for their establishment
• How their assembly is realized (in ER and plasma membrane)
• How they operate at the plasma membrane (in concert with other assemblies)
• How they realize the enormous specificity of signaling in both time and space
• How they endow signaling with the activity-dependent dynamics required for memory formation and/or adaptation to external boundaries and
• How impairment of their function (in assembly and/or operation) leads to disease(s).

For this purpose, we use a multidisciplinary approach combining high resolution proteomics (proprietary biochemistry, mass spectrometry), complexome analysis (csBN-MS), electrophysiology (various techniques in cells and tissue slices), 2-photon imaging and fluorescence microscopy, electron microscopy (conventional, freeze-fracture replicas), structural biology (NMR, cryo-EM).

Keywords

Protein complexes, mass spectrometry, proteomics, patch-clamp, complexome, csBN-MS, freeze-fracture replicas, protein assembly, protein-protein interactions

10 selected publications

• Mitochondrial complexome reveals quality-control pathways of protein import.
  Schulte U, den Brave F, Haupt A, Gupta A, Song J, Müller CS, Engelke J, Mishra S, Mårtensson C, Ellenrieder L, Priesnitz C, Straub SP, Doan KN, Kulawiak B, Bildl W, Rampelt H, Wiedemann N, Pfanner N*, Fakler B*, Becker T (2023).
  Nature. 614(7946):153-159.
• Subunit composition, molecular environment, and activation of native TRPC channels encoded by their interactomes.
  Kollewe A, Schwarz Y, Oleinikov K, Raza A, Haupt A, Wartenberg P, Wyatt A, Boehm U, Ectors F, Bildl W, Zolles G, Schulte U, Bruns D, Flockerzi V, Fakler B (2022).
  Neuron. 110(24):4162-4175.e7.
• An ER assembly line of AMPA-receptors controls excitatory neurotransmission and its plasticity.
  Schwenk J, Boudkkazi S, Kocylowski M, Brechet A, Zolles G, Bus T, Costa K, Kollewe A, Jordan J, Bank J, Bildl W, Sprengel R, Kulik A, Roeper J, Schulte U, Fakler B (2019)
  Neuron 104: 680-692.
• Neuroplastin and basigin are essential auxiliary subunits of plasma membrane Ca2+-ATPases and key regulators of Ca2+ Clearance.
  Schmidt N, Kollewe A, Constantin CE, Henrich S, Ritzau-Jost A, Bildl W, Saalbach A, Hallermann S, Kulik A, Fakler B*, Schulte U* (2017).
  Neuron 96, 827-838.
• Modular composition and dynamics of native GABAB receptors identified by high-resolution proteomics.
  Schwenk J, Perez-Garci E, Schneider A, Kollewe A, Gauthier-Kemper A, Fritzius T, Raveh A, Dinamarca MC, Hanuschkin A, Bildl W, Klingauf J, Gassmann M, Schulte U, Bettler B, Fakler B (2016).
  Nat. Neurosci. 19, 233-42.
• Regional diversity and developmental dynamics of the AMPA-receptor proteome in the mammalian brain.
  Schwenk J, Baehrens D, Haupt A, Bildl W, Boudkkazi S, Roeper J, Fakler B, Schulte U (2014).
  Neuron. 84(1):41-54.
• High-resolution proteomics unravel architecture and molecular diversity of native AMPA receptor complexes.
  Schwenk J, Harmel N, Brechet A, Zolles G, Berkefeld H, Muller CS, Bildl W, Baehrens D, Huber B, Kulik A, Klöcker N, Schulte U*, Fakler B* (2012).
  Neuron 74, 621-33.
• Native GABAB receptors are heteromultimers with a family of auxiliary subunits.
  Schwenk J, Metz M, Zolles G, Turecek R, Fritzius T, Bildl W, Tarusawa E, Kulik A, Unger A, Ivankova A, Seddik R, Tiao JY, Rajalu M, Trojanova J, Rohde V, Gassmann M, Schulte U, Fakler B*, Bettler B* (2010).
  Nature 13;465, 231-5.
• Functional proteomics identify cornichon proteins as auxiliary subunits of AMPA receptors.
  Schwenk J, Harmel N, Zolles G, Bildl W, Kulik A, Heimrich B, Chisaka O, Jonas P, Schulte U, Fakler B*, Klöcker N* (2009).
  Science 323, 1313-9.
• BKCa-Cav channel complexes mediate rapid and localized Ca2+-activated K+ signaling.
  Berkefeld H, Sailer CA, Bildl W, Rohde V, Thumfart JO, Eble S, Klugbauer N, Reisinger E, Bischofberger J, Oliver D, Knaus HG, Schulte U, Fakler B (2006).
  Science 314, 615-2.

* corresponding author