Changes in the intracellular calcium concentration play a critical role in cellular responses to cues from the extracellular environment. One influx route for slower and long lasting changes in [Ca2+] involve the release of Ca2+ from intracellular stores and entry of extracellular Ca2+. Depletion of distinct Ca2+ stores results in store-operated Ca2+ entry (SOCE). The best studied SOC current is the Calcium Release Activated Calcium current (ICRAC). ICRAC plays an important role in many cellular processes e.g. gene expression and cell proliferation.
Our group works on the molecular components of ICRAC (CRACM = Orai1, 2 und 3 Ca2+ channels, sensor proteins (stromal interaction molecule) STIM1 und STIM2). We are interested in structure/function relationship and dysregulation of SOCE signals in the pathophysiology of cancer and immune disease.
The main focus of our group is the transient receptor potential melastatin-4 channel (TRPM4). We and others demonstrated that TRPM4 expression levels are elevated in human prostate cancer tissue. In prostate cancer cells, TRPM4-mediated Na+ influx can depolarize the membrane potential, decreasing the driving force for Ca2+ and reducing SOCE signals as a feedback mechanism. In addition, TRPM4 contributes to migration of prostate cancer cells, which is one of the initial steps to metastasis. Our group aims to investigate the physiological and pathophysiological consequences of TRPM4 impairments in prostate cancer cells.
- Physiology/Pathophysiology of ion channels
- Pharmacology of Ca2+ signals, STIM/Orai, TRPM4
- Ion channels as future therapeutic targets
- Electrophysiology, BioImaging, Ca2+ Imaging, cell assays
- Human primary prostate epithelial cells/tissues
- Immune system
- Prostate cancer
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Holzmann, C., T. Kilch, S. Kappel, K. Dorr, V. Jung, M. Stockle, I. Bogeski and C. Peinelt 2015. Differential redox regulation of ca(2+) signaling and viability in normal and malignant prostate cells. Biophys. J. 109, 1410-1419.
Holzmann, C., S. Kappel, T. Kilch, M.M. Jochum, S.K. Urban, V. Jung, M. Stockle, K. Rother, M. Greiner and C. Peinelt 2015. Transient receptor potential melastatin 4 channel contributes to migration of androgen-insensitive prostate cancer cells. Oncotarget.
Alansary, D., T. Kilch, C. Holzmann, C. Peinelt, M. Hoth and A. Lis 2014. The minimal requirements to use calcium imaging to analyze ICRAC. Cold Spring Harb Protoc. 2014, pdb.prot073262.
Alansary, D., T. Kilch, C. Holzmann, C. Peinelt, M. Hoth and A. Lis 2014. Measuring endogenous ICRAC and ORAI currents with the patch-clamp technique. Cold Spring Harb Protoc. 2014, pdb.prot073254.
Alansary, D., T. Kilch, C. Holzmann, C. Peinelt, M. Hoth and A. Lis 2014. Patch-clamp measurement of ICRAC and ORAI channel activity. Cold Spring Harb Protoc. 2014, pdb.top066795.
Beck, A., A. Fleig, R. Penner and C. Peinelt 2014. Regulation of endogenous and heterologous ca(2+) release-activated ca(2+) currents by pH. Cell Calcium. 56, 235-243.
Kilch, T., D. Alansary, M. Peglow, K. Dorr, G. Rychkov, H. Rieger, C. Peinelt and B.A. Niemeyer 2013. Mutations of the Ca2+-sensing stromal interaction molecule STIM1 regulate Ca2+ influx by altered oligomerization of STIM1 and by destabilization of the Ca2+ channel Orai1. J. Biol. Chem. 288, 1653-1664.
Holzmann, C., T. Kilch, S. Kappel, A. Armbruster, V. Jung, M. Stockle, I. Bogeski, E.C. Schwarz and C. Peinelt 2013. ICRAC controls the rapid androgen response in human primary prostate epithelial cells and is altered in prostate cancer. Oncotarget. 4, 2096-2107.
Carreras-Sureda, A., G. Cantero-Recasens, F. Rubio-Moscardo, K. Kiefer, C. Peinelt, B.A. Niemeyer, M.A. Valverde and R. Vicente 2013. ORMDL3 modulates store-operated calcium entry and lymphocyte activation. Hum. Mol. Genet. 22, 519-530.
Stanisz, H., A. Stark, T. Kilch, E.C. Schwarz, C.S. Muller, C. Peinelt, M. Hoth, B.A. Niemeyer, T. Vogt and I. Bogeski 2012. ORAI1 ca(2+) channels control endothelin-1-induced mitogenesis and melanogenesis in primary human melanocytes. J. Invest. Dermatol. 132, 1443-1451.
Bogeski, I., C. Kummerow, D. Al-Ansary, E.C. Schwarz, R. Koehler, D. Kozai, N. Takahashi, C. Peinelt, D. Griesemer, M. Bozem, Y. Mori, M. Hoth and B.A. Niemeyer 2010. Differential redox regulation of ORAI ion channels: A mechanism to tune cellular calcium signaling. Sci. Signal. 3, ra24.
Bogeski, I., D. Al-Ansary, B. Qu, B.A. Niemeyer, M. Hoth and C. Peinelt 2010. Pharmacology of ORAI channels as a tool to understand their physiological functions. Expert Rev. Clin. Pharmacol. 3, 291-303.
Lis, A., S. Zierler, C. Peinelt, A. Fleig and R. Penner 2010. A single lysine in the N-terminal region of store-operated channels is critical for STIM1-mediated gating. J. Gen. Physiol. 136, 673-686.
Peinelt, C., A. Beck, M.K. Monteilh-Zoller, R. Penner and A. Fleig 2009. IP(3) receptor subtype-dependent activation of store-operated calcium entry through I(CRAC). Cell Calcium. 45, 326-330.
Peinelt, C., A. Lis, A. Beck, A. Fleig and R. Penner 2008. 2-aminoethoxydiphenyl borate directly facilitates and indirectly inhibits STIM1-dependent gating of CRAC channels. J. Physiol. 586, 3061-3073.
Parvez, S., A. Beck, C. Peinelt, J. Soboloff, A. Lis, M. Monteilh-Zoller, D.L. Gill, A. Fleig and R. Penner 2008. STIM2 protein mediates distinct store-dependent and store-independent modes of CRAC channel activation. Faseb J. 22, 752-761.
Lis, A., C. Peinelt, A. Beck, S. Parvez, M. Monteilh-Zoller, A. Fleig and R. Penner 2007. CRACM1, CRACM2, and CRACM3 are store-operated Ca2+ channels with distinct functional properties. Curr. Biol. 17, 794-800.
Peinelt, C., M. Vig, D.L. Koomoa, A. Beck, M.J. Nadler, M. Koblan-Huberson, A. Lis, A. Fleig, R. Penner and J.P. Kinet 2006. Amplification of CRAC current by STIM1 and CRACM1 (Orai1). Nat. Cell Biol. 8, 771-773.
Vig, M., A. Beck, J.M. Billingsley, A. Lis, S. Parvez, C. Peinelt, D.L. Koomoa, J. Soboloff, D.L. Gill, A. Fleig, J.P. Kinet and R. Penner 2006. CRACM1 multimers form the ion-selective pore of the CRAC channel. Curr. Biol. 16, 2073-2079.
Vig, M., C. Peinelt, A. Beck, D.L. Koomoa, D. Rabah, M. Koblan-Huberson, S. Kraft, H. Turner, A. Fleig, R. Penner and J.P. Kinet 2006. CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science. 312, 1220-1223.
Peinelt, C. and H.J. Apell 2005. Kinetics of Ca2+ binding to the SR ca-ATPase in the E1 state. Biophys. J. 89, 2427-2433.
Peinelt, C. and H.J. Apell 2004. Time-resolved charge movements in the sarcoplasmatic reticulum ca-ATPase. Biophys. J. 86, 815-824.
Peinelt, C. and H.J. Apell 2003. Time-resolved partial reactions of the SR ca-ATPase investigated with a fluorescent styryl dye. Ann. N. Y. Acad. Sci. 986, 325-326.
Peinelt, C. and H.J. Apell 2002. Kinetics of the ca(2+), H(+), and mg(2+) interaction with the ion-binding sites of the SR ca-ATPase. Biophys. J. 82, 170-181.