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Cardiovascular and Hemostatic Disorders: Role of STIM and Orai Proteins in Vascular Disorders

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Store-Operated Ca²⁺ Entry (SOCE) Pathways

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 993))

Abstract

Store-operated Ca2+ entry (SOCE) mediated by STIM and Orai proteins is a highly regulated and ubiquitous signaling pathway that plays an important role in various cellular and physiological functions. Endoplasmic reticulum (ER) serves as the major site for intracellular Ca2+ storage. Stromal Interaction Molecule 1/2 (STIM1/2) sense decrease in ER Ca2+ levels and transmits the message to plasma membrane Ca2+ channels constituted by Orai family members (Orai1/2/3) resulting in Ca2+ influx into the cells. This increase in cytosolic Ca2+ in turn activates a variety of signaling cascades to regulate a plethora of cellular functions. Evidence from the literature suggests that SOCE dysregulation is associated with several pathophysiologies, including vascular disorders. Interestingly, recent studies have suggested that STIM proteins may also regulate vascular functions independent of their contribution to SOCE. In this updated book chapter, we will focus on the physiological role of STIM and Orai proteins in the vasculature (endothelial cells and vascular smooth muscle cells). We will further retrospect the literature implicating a critical role for these proteins in vascular disease.

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Acknowledgments

Mohamed Trebak is supported by R01HL123364, R01HL097111, and R21AG050072 grants from the NIH, grant NPRP8-110-3-021 from the Qatar National Research Fund (GNRF), and grant 14GRNT18880008 from the AHA. Rajender K Motiani is an INSPIRE Faculty supported by the Department of Science and Technology, India. The authors have no conflict of interests to declare.

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Authors and Affiliations

  1. Systems Biology Group, CSIR-Institute of Genomics and Integrative Biology, Mathura Road, New Delhi, 110020, India

    Jyoti Tanwar & Rajender K. Motiani

  2. Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA, 17033, USA

    Mohamed Trebak

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  1. Jyoti Tanwar
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  2. Mohamed Trebak
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  3. Rajender K. Motiani
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Correspondence to Mohamed Trebak or Rajender K. Motiani .

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  1. Institute of Biophysics, Medical University of Graz, Graz, Austria

    Klaus Groschner

  2. Institute of Molecular Biology and Biochemistry, Medical University of Graz, Graz, Austria

    Wolfgang F. Graier

  3. Institute of Biophysics, Johannes Kepler University Linz, Linz, Austria

    Christoph Romanin

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Tanwar, J., Trebak, M., Motiani, R.K. (2017). Cardiovascular and Hemostatic Disorders: Role of STIM and Orai Proteins in Vascular Disorders. In: Groschner, K., Graier, W., Romanin, C. (eds) Store-Operated Ca²⁺ Entry (SOCE) Pathways. Advances in Experimental Medicine and Biology, vol 993. Springer, Cham. https://doi.org/10.1007/978-3-319-57732-6_22

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