פרופ' כורת הירשברג

Professor, Department of Pathology, Sackler Faculty of Medicine

Intracellular Membrane Trafficking

Our laboratory focuses on investigating the protein and membrane interactions that delineate membrane transport processes. We are especially interested in the functions of cargo recognition, concentration and targeted delivery to distinct cellular membranes. All transport processes use the membrane as their final substrate for example: fusion, budding, generation of distinct domains and the establishment of curvature. Combined, these functions shape the cellular transport machinery, one of the major systems that maintain homeostasis communication and response to the external environment in health and disease. 

To understand these processes in detail, one must recognize that protein–protein as well as protein-lipid interactions are involved. Studying the later, namely protein-lipid interaction is challenging since these interactions are less specific and complex experimental systems are to be used. In other words, to study the association between a protein to its proximal native lipid environment, membranes cannot be disrupted or solubilized.

In our laboratory, we combine traditional biochemical analysis with live cell imaging and quantitative kinetic modeling to gather information on the dynamic features of the cellular secretory transport machinery.  Experiments are carried out using expression of fluorescent protein tagged proteins in living intact cells using laser scanning confocal microscopes. We use a range of state-of-the-art experimental setups such as: Time-lapse imaging, three-dimensional reconstruction, multicolor imaging, photobleaching/photoactivation–based manipulations and Bi-Molecular fluorescent complementation (BiFC). Kinetic modeling and simulation software is often used to extract values of kinetic coefficients or to perform model testing from the wealth of information hidden in the images sequences.

Wagner V, Elke Stadelmeyer E, Riederer M, Regitnig P, Gorischek A, DeVvaney T, Schmidt K, Tritthart HA, Hirschberg K, Bauernhofer T, Schreibmayer W. Cloning and characterization of GIRK1 variants resulting from alternative RNA editing of the KCNJ3 gene transcript in a human breast cancer cell line. J Cell Biochem. J Cell Biochem.110, 598-608, 2010.

Alfaguter-Azoulay I, Yaffe Y, Licht-Murava A, Urbanska M, Jaworski J, Pietrokovski S, Hirschberg K, Eldar-Finkelman H. Distinct molecular regulation of GSK-3alpha isozyme controlled by its N-terminal region. Functional role in calcium/calpain signaling. J Biol Chem. 286, 15, 13470-80. 2011.

Benjamin S, Weidberg H, Rapaport D, Pekar O, Nudelman M, Segal D, Hirschberg K, Katzav S, Ehrlich M, Horowitz M. EHD2 mediates trafficking from the plasma membrane by modulating Rac1 activity. Biochemical J. 439:433-42. 2011.

Yaffe Y, Shepshelovitch J, Yeheskel A, Shmerling H, Kwiatek JM, KaGaus K, Pasmanik-Chor M, Hirschberg K. The MARVEL transmembrane domain of Occludin mediates oligomerization and targeting to the basolateral surface in epithelia. J Cell Sci. 125:3545-56. 2012.

Nevo-Yassaf I, Yaffe Y, Asher M, Ravid O, Eizenberg S, Henis YI, Nahmias Y, Hirschberg K, Sklan EH. A role for TBC1D20 and Rab1 in Hepatitis C virus replication via interaction with LD bound NS5A. J Virol, 86:6491-502. 2012

David N, Yaffe Y, Hagoel L, Elazar M, Glenn JS, Hirschberg K, Sklan EH. The interaction between the Hepatitis C proteins NS4B and NS5A is involved in viral replication. Virology. 475C:139-149. 2014

Yaffe Y, Hagger I , Nevo Yassaf I, Shepshelovitch J, Sklan EH, Elkabetz Y, Yeheskel A, Pasmanik-Chor M, Benzing C, Macmillan A, Gaus K, Eshed-Eisenbach Y, Peles E, Hirschberg K. The myelin proteolipid Plasmolipin, forms oligomers and induces liquid ordered membranes in the Golgi apparatus. J. Cell Science 128, 2293-302. 2015

• 2012-2016 Israel Science Foundation (ISF) Grant, Surface expression of proteins is regulated by sorting and selection in endoplasmic reticulum exit sites and in the Golgi apparatus
• 2016 Jerome Lejeune Foundation