Page 16 - Rappaport Institute Magazine 2024

BIOCHEMISTRY
Raz Palty, PhD
Associate Professor of Biochemistry
PhD, 2010 – Ben-Gurion University of The Negev, Israel
Calcium signaling in health and disease
Intracellular calcium ions (Ca2+) are likely the most important signaling molecules within mammalian cells. The primary focus of research in our laboratory revolves around unraveling the molecular intricacies of Ca2+ signaling in and around intracellular organelles. Our keen interest lies in deciphering the mechanisms responsible for generation of these signals and understanding their contributions to human physiology in both normal and diseased states. At present, our efforts are dedicated to the investigation of a fascinating cellular phenomenon termed store-operated calcium entry. This process is initiated by the activation of calcium channels in the endoplasmic reticulum (ER), leading to the depletion of intracellular calcium stores. Subsequently, this depletion triggers the opening of calcium channels in the plasma membrane (PM). The calcium signals emanating from store-operated calcium entry play a particularly pivotal role in the immune functions of T lymphocytes. Notably, mutations causing loss of function in the STIM1 or Orai1 genes result in a severe form of immunodeficiency in humans.
Our overarching goal is to attain a comprehensive understanding of the mechanisms governing the regulation of channel opening through the coupling of STIM and Orai proteins, as well as the impact of accessory proteins on this process. To achieve this, we employ a multidisciplinary approach, integrating genetic, protein, and chemical engineering with patch-clamp electrophysiology and advanced high-resolution imaging techniques.
Selected Publications
ˆ Raz Palty, William F. Silverman, Michal Hershfinkel, Teresa Caporale, Stefano L. Sensi, Julia Parnis, Christiane Nolte, Daniel Fishman, Varda Shoshan-Barmatz, Sharon Herrmann, Daniel Khananshvili, and Israel Sekler. “NCLX is an essential component of mitochondrial Na+/Ca2+ exchange” PNAS, 2010, 107(1):436-41.
ˆ Raz Palty, Adi Raveh, Ido Kaminsky, Ruth Meller and Eitan Reuveny. “SARAF Inactivates the Store Operated Calcium Entry Machinery to Prevent Excess Calcium Refilling” Cell, 2012, 149(2):425-38.
* Research Highlight: Stop refilling Ca2+ stores. Nat Rev Mol Cell Biol.
ˆ Elia Zomot, Hadas Achildiev, Inbal Dagan, Ruslana Militsin and Raz Palty. “Bidirectional regulation of Calcium-Release Activated Calcium (CRAC) channel by SARAF” Journal of Cell Biology, 2021 Dec 6;220(12)
ˆ Ronald Udasin, Anwesha Sil, Elia Zomot, Hadas Achildiev Cohen, Jozafina Haj, Nurit
ˆ Engelmayer, Shaya Lev, Alexander M Binshtok, Yuval Shaked, Michael A Kienzler and Raz Palty “Photopharmacological modulation of native CRAC channels using azoboronate photoswitches” PNAS, 2022 Mar 29;119(13)
Grants and Awards
2018 - 2022 Israel Science Foundation (ISF) – Personal research grant
2020 - 2024 U.S.-Israel Binational Science Foundation (BSF)-U.S. National Science Foundation (NSF) – Research grant (in collaboration with Michael Kienzler)
2022 - 2027 Israel Science Foundation (ISF) – Personal research grant Collaborators
Ehud Isacoff - University of California Berkeley
Michael Kienzler – University of Connecticut
Daniel L Minor – University of California San Francisco
Eitan Reuveny – Weismann Institute of Science
Alexander Binshtok - Hebrew University
Benny Kimelfeld – Technion
Andreas H Guse – University of Hamburg
razpalty@technion.ac.il
Raz Palty Lab
Image shows the plasma membrane of a human kidney cell expressing STIM1 (Green) and Orai1 (Red), at rest (upper panel) and following activation of store operated calcium entry (bottom panel).