• Alexei V. TepikinEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 993)


In the title of this part of the book, the tail is wagging not just in a single dog but multiple dogs; in other words, a single process SOCE (tail) somehow involves a cross talk of (wagging) large and powerful organelle and cellular compartments (dogs). So how is this possible? Is this really necessary? Is the title actually appropriate?

SOCE is a rather special process, it allows efficient signaling based on a ubiquitous second messenger (Ca2+) in multiple cell and tissue types, it has specific signaling modality (i.e., some downstream reactions depend specifically on SOCE and not just on global Ca2+ increase), it is vital for the normal functioning of multiple types of cells and tissues, and when misregulated it induces important pathological processes. The reader hopefully agree that such an important “tail” is more appropriate for a kangaroo than for a Chihuahua and that it has awesome wagging capacity.


Store-operated Ca2+ entry ER-PM junctions Membrane contact sites Organelle contact sites Ca2+ signaling Ca2+ influx 


  1. Ambudkar IS, de Souza LB, Ong HL (2016) TRPC1, Orai1, and STIM1 in SOCE: friends in tight spaces. Cell Calcium. doi: 10.1016/j.ceca.2016.12.009 Google Scholar
  2. Barrow SL, Voronina SG, da Silva XG, Chvanov MA, Longbottom RE, Gerasimenko OV, Petersen OH, Rutter GA, Tepikin AV (2008) ATP depletion inhibits Ca2+ release, influx and extrusion in pancreatic acinar cells but not pathological Ca2+ responses induced by bile. Pflugers Arch 455:1025–1039CrossRefPubMedGoogle Scholar
  3. Baughman JM, Perocchi F, Girgis HS, Plovanich M, Belcher-Timme CA, Sancak Y, Bao XR, Strittmatter L, Goldberger O, Bogorad RL, Koteliansky V, Mootha VK (2011) Integrative genomics identifies MCU as an essential component of the mitochondrial calcium uniporter. Nature 476:341–345CrossRefPubMedPubMedCentralGoogle Scholar
  4. Bogeski I, Kilch T, Niemeyer BA (2012) ROS and SOCE: recent advances and controversies in the regulation of STIM and Orai. J Physiol 590:4193–4200CrossRefPubMedPubMedCentralGoogle Scholar
  5. Carrasco S, Meyer T (2011) STIM proteins and the endoplasmic reticulum-plasma membrane junctions. Annu Rev Biochem 80:973–1000CrossRefPubMedPubMedCentralGoogle Scholar
  6. De Stefani D, Raffaello A, Teardo E, Szabo I, Rizzuto R (2011) A forty-kilodalton protein of the inner membrane is the mitochondrial calcium uniporter. Nature 476:336–340CrossRefPubMedPubMedCentralGoogle Scholar
  7. De Stefani D, Patron M, Rizzuto R (2015) Structure and function of the mitochondrial calcium uniporter complex. Biochim Biophys Acta 1853:2006–2011CrossRefPubMedPubMedCentralGoogle Scholar
  8. Feske S, Gwack Y, Prakriya M, Srikanth S, Puppel SH, Tanasa B, Hogan PG, Lewis RS, Daly M, Rao A (2006) A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function. Nature 441:179–185CrossRefPubMedGoogle Scholar
  9. Frieden M, Arnaudeau S, Castelbou C, Demaurex N (2005) Subplasmalemmal mitochondria modulate the activity of plasma membrane Ca2+-ATPases. J Biol Chem 280:43198–43208CrossRefPubMedGoogle Scholar
  10. Glitsch MD, Bakowski D, Parekh AB (2002) Store-operated Ca2+ entry depends on mitochondrial Ca2+ uptake. EMBO J 21:6744–6754CrossRefPubMedPubMedCentralGoogle Scholar
  11. Hogan PG, Lewis RS, Rao A (2010) Molecular basis of calcium signaling in lymphocytes: STIM and ORAI. Annu Rev Immunol 28:491–533CrossRefPubMedPubMedCentralGoogle Scholar
  12. Hoth M, Fanger CM, Lewis RS (1997) Mitochondrial regulation of store-operated calcium signaling in T lymphocytes. J Cell Biol 137:633–648CrossRefPubMedPubMedCentralGoogle Scholar
  13. Kamer KJ, Mootha VK (2015) The molecular era of the mitochondrial calcium uniporter. Nat Rev Mol Cell Biol 16:545–553CrossRefPubMedGoogle Scholar
  14. Lee KP, Yuan JP, So I, Worley PF, Muallem S (2010) STIM1-dependent and STIM1-independent function of transient receptor potential canonical (TRPC) channels tunes their store-operated mode. J Biol Chem 285:38666–38673CrossRefPubMedPubMedCentralGoogle Scholar
  15. Liou J, Kim ML, Heo WD, Jones JT, Myers JW, Ferrell JE Jr, Meyer T (2005) STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx. Curr Biol 15:1235–1241CrossRefPubMedPubMedCentralGoogle Scholar
  16. Luik RM, Wu MM, Buchanan J, Lewis RS (2006) The elementary unit of store-operated Ca2+ entry: local activation of CRAC channels by STIM1 at ER-plasma membrane junctions. J Cell Biol 174:815–825CrossRefPubMedPubMedCentralGoogle Scholar
  17. Malli R, Frieden M, Osibow K, Zoratti C, Mayer M, Demaurex N, Graier WF (2003) Sustained Ca2+ transfer across mitochondria is Essential for mitochondrial Ca2+ buffering, sore-operated Ca2+ entry, and Ca2+ store refilling. J Biol Chem 278:44769–44779CrossRefPubMedGoogle Scholar
  18. Montalvo GB, Artalejo AR, Gilabert JA (2006) ATP from subplasmalemmal mitochondria controls Ca2+-dependent inactivation of CRAC channels. J Biol Chem 281:35616–35623CrossRefPubMedGoogle Scholar
  19. Nunes P, Cornut D, Bochet V, Hasler U, Oh-Hora M, Waldburger JM, Demaurex N (2012) STIM1 juxtaposes ER to phagosomes, generating Ca(2)(+) hotspots that boost phagocytosis. Curr Biol 22:1990–1997CrossRefPubMedGoogle Scholar
  20. Okeke E, Dingsdale H, Parker T, Voronina S, Tepikin AV (2016) Endoplasmic reticulum-plasma membrane junctions: structure, function and dynamics. J Physiol (Lond) 594:2837–2847CrossRefGoogle Scholar
  21. Prakriya M, Feske S, Gwack Y, Srikanth S, Rao A, Hogan PG (2006) Orai1 is an essential pore subunit of the CRAC channel. Nature 443:230–233CrossRefPubMedGoogle Scholar
  22. Prinz WA (2014) Bridging the gap: membrane contact sites in signaling, metabolism, and organelle dynamics. J Cell Biol 205:759–769CrossRefPubMedPubMedCentralGoogle Scholar
  23. Putney JW Jr (2007) Recent breakthroughs in the molecular mechanism of capacitative calcium entry (with thoughts on how we got here). Cell Calcium 42:103–110CrossRefPubMedPubMedCentralGoogle Scholar
  24. Reinisch KM, De Camilli P (2016) SMP-domain proteins at membrane contact sites: structure and function. Biochim Biophys Acta 1861:924–927CrossRefPubMedGoogle Scholar
  25. Roos J, DiGregorio PJ, Yeromin AV, Ohlsen K, Lioudyno M, Zhang S, Safrina O, Kozak JA, Wagner SL, Cahalan MD, Veliçelebi G, Stauderman KA (2005) STIM1, an essential and conserved component of store-operated Ca2+ channel function. J Cell Biol 169:435–445CrossRefPubMedPubMedCentralGoogle Scholar
  26. Samanta K, Douglas S, Parekh AB (2014) Mitochondrial calcium uniporter MCU supports cytoplasmic Ca2+ oscillations, store-operated Ca2+ entry and Ca2+-dependent gene expression in response to receptor stimulation. PLoS One 9:e101188CrossRefPubMedPubMedCentralGoogle Scholar
  27. Vig M, Peinelt C, Beck A, Koomoa DL, Rabah D, Koblan-Huberson M, Kraft S, Turner H, Fleig A, Penner R, Kinet JP (2006) CRACM1 is a plasma membrane protein essential for store-operated Ca2+ entry. Science 312:1220–1223CrossRefPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.The Physiological Laboratory, Department of Cellular and Molecular Physiology, Institute of Translational MedicineUniversity of LiverpoolLiverpoolUK

Personalised recommendations