Dr. Maximilian Ulbrich
Research in the Ulbrich Lab is focused on deciphering composition and dynamics of membrane proteins using novel single molecule techniques in living cells. In particular, we are curious how extracellular cues are processed by receptors in the cell membrane to trigger an intracellular signaling cascade. Examples are GPCR signaling or activation of immune cells.
We use fluorescent proteins or organic dyes to label the proteins of interest, and express them in Xenopus oocytes or mammalian cell lines. Single fluorescent proteins can be spatially resolved when the expression density is low enough, and it then becomes possible to count individual molecules or track their movement in the membrane. Co-localization of fluorescent tags of different colors can indicate the interaction of different proteins.
Currently we are investigating the role of G protein-coupled receptor oligomerization and their interactions with downstream signaling proteins. Although many GPCRs are shown to function well as monomers, a tendency to form dimers was reported frequently. However, the physiological role for dimerization is still unclear for most GPCRs. On the other hand, some GPCRs can only function as dimers because different functional units are distributed between the two subunits. One open question we want to solve is if a shift of the monomer-dimer equilibrium plays a role during signaling.
Another topic we are interested in is the association of synaptic glutamate receptors with auxiliary subunits. Nerve cells regulate the composition of glutamate receptors depending on the cell type and its activity. Many other proteins interact with the glutamate receptor to modulate its function and regulate trafficking to the synapse. We are trying to determine how many auxiliary subunits are associated with the glutamate receptor, to understand the stability of these interactions and if they compete for common binding sites.
10 selected publications:
- A CD36 ectodomain mediates insect pheromone detection via a putative tunnelling mechanism.
Gomez-Diaz C, Bargeton B, Abuin L, Bukar N, Reina JH, Bartoi T, Graf M, Ong H, Ulbrich MH, Masson JF, Benton R.
Nat Commun. 7: 11866 (2016).
- Acid-sensing ion channel (ASIC) 1a/2a heteromers have a flexible 2:1/1:2 stoichiometry.
Bartoi T, Augustinowski K, Polleichtner G, Gründer S, Ulbrich MH.
Proc Natl Acad Sci U S A. 111: 8281-8286 (2014).
- AMPA receptor⁄TARP stoichiometry visualized by single molecule subunit counting.
Hastie P, Ulbrich MH, Wang H, Arant RJ, Lau AG, Zhang Z, Isacoff EY, Chen L.
Proc Natl Acad Sci U S A. 110: 5163-5168 (2013).
- Molecular mechanism of the assembly of an acid-sensing receptor ion channel complex.
Yu Y, Ulbrich MH, Li MH, Dobbins S, Zhang WK, Tong L, Isacoff EY, Yang J.
Nat Commun 3, Article number: 1252 (2012).
- Stoichiometry and gating of the KCNQ1-KCNE1 ion channel complex.
Nakajo K, Ulbrich MH, Kubo Y, Isacoff EY.
Proc Natl Acad Sci U S A. 107:18862-18867 (2010).
- The opening of the two pores of the Hv1 voltage-gated proton channel is tuned by cooperativity.
Tombola F, Ulbrich MH, Kohout SC, Isacoff EY.
Nat Struct Mol Biol. 17:44-50 (2010).
- Rules of engagement for NMDA receptor subunits.
Ulbrich MH, Isacoff EY.
Proc Natl Acad Sci U S A. 105:14163-14168 (2008).
- The voltage-gated proton channel Hv1 has two pores, each controlled by one voltage sensor.
Tombola F, Ulbrich MH, Isacoff EY.
Neuron 58:546-556 (2008).
- Subunit organization and functional transitions in Ci-VSP.
Kohout SC, Ulbrich MH, Bell SC, Isacoff EY.
Nat Struct Mol Biol. 15:106-108 (2008).
- Subunit counting in membrane-bound proteins.
Ulbrich MH, Isacoff EY.
Nature Methods 4:319-312 (2007).