Ruprecht-Karls-Universitšt Heidelberg

Matthias Seedorf
Project Group Leader in the
ZMBH

ZMBH
Im Neuenheimer Feld 282
69120 Heidelberg, Germany
Tel.: + 49-6221 54 8299.
Fax: +49-6221 54 5892.
m.seedorf@zmbh.uni-heidelberg.de


Coupling of ER and plasma membrane


Organelles communicate and coordinate cellular functions through membrane contact sites. We are interested in the common principles of membrane contact formation between the endoplasmic reticulum (ER) and the plasma membrane (PM). Some integral membrane proteins of the cortical ER interact with phosphoinositide lipids (PIPs) at the cytosolic face of the PM and this interaction recruits ER to the PM. In yeast the polytopic membrane protein Ist2 fulfils this function. Ist2 determines the distance between cortical ER and PM creating a specific microenvironment between these membranes.


The formation of ER-PM contact sites by ER resident membrane proteins that bind PM lipids is conserved. STIM1 and the closely related protein STIM2 in mammalian cells combine ER-PM contact formation with a function as ER calcium sensor. In response to calcium depletion STIM proteins become activated, bind PIPs at the PM and open calcium channels in the PM. By this STIM1 and STIM2 contribute to calcium signaling and homeostasis.


We use the model system Saccharomyces cerevisiae, in order to

  • Study how Ist2 in the cortical ER influences the spatial organization and function of proteins in the PM, e.g. specific H+/amino acid symporters.

  • Measure the effect of Ist2 on transient pH-gradients across the ER membrane.

  • Characterize the putative function of Ist2 as chloride channel based on its similarity to members of the TMEM16/ANO protein family. 

In addition, we employ mammalian tissue culture in order to

  • Investigate signals that retain STIM1 in specific domains of the ER during interphase and follow the fate of STIM1 during mitosis.

  • Study the dynamics of ER-PM contacts and analyze the contribution of the cytoskeleton and other factors to the formation of cortical ER.

  • Characterize differences in the PM lipid-binding signals in STIM1 and STIM2 and study how the activity of these lipid-binding signals is regulated.  

Selected publications

Wolf, W., Kilic, A., Schrul, B., Lorenz, H., Schwappach, B. and M. Seedorf (2012). Yeast Ist2 recruits the endoplasmic reticulum to the plasma membrane and creates a ribosome-free membrane microcompartment. PLoS ONE 7: e39703.

Ercan, E., Chung, S-H., Bhardwaj, R. and M. Seedorf (2012). Di-arginine signals and the K-rich domain retain the Ca2+ sensor STIM1 in the endoplasmic reticulum. Traffic, 13, 992-1003.

Ercan, E., Momburg, F., Engel, E., Temmerman, K., Nickel, W. and M. Seedorf (2009). A conserved, lipid-mediated sorting mechanism of yeast Ist2 and mammalian STIM proteins to the peripheral ER. Traffic 10:1802-1818.

Fischer, M.A., Temmerman, K., Ercan, E., Nickel, W. and M. Seedorf (2009). Binding of the plasma membrane lipids recruits the yeast integral membrane protein Ist2 to the cortical ER. Traffic, 10, 1084-1097.

Maass, K., Fischer, M.A., Seiler, M., Temmerman, K., Nickel, W. and M. Seedorf (2009). A signal comprising a basic cluster and an amphipathic α-helix interacts with lipids and is required for the transport of Ist2 to the yeast cortical ER. Journal of Cell Science, 122, 625- 635.

Nickel, W. and M. Seedorf (2008). Unconventional Mechanisms of Protein Transport to the Cell Surface of Eukaryotic Cells. Annual Review of Cell and Developmental Biology, 24, 287-3082.

Jüschke, C., Wächter, A., Schwappach, B. and Seedorf, M. (2005). SEC18/NSF-independent, protein-sorting pathway from the yeast cortical ER to the plasma membrane. J. Cell Biol. 169:613-622.