The location of InsP3 receptors in Purkinje cells of murine cerebellum does not supports a direct interaction in the transfer of calcium ions between ER and mitochondria


Submitted: 23 June 2021
Accepted: 6 August 2021
Published: 31 August 2021
Abstract Views: 780
PDF: 288
HTML: 24
Publisher's note
All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

Authors

The inositol-3-phosphate receptors (IP3Rs) of cerebellar Purkinje cells are located in abundant, large stacks of endoplasmic reticulum (ER) cisternae. Using thin section electron microscopy, we identify very frequent associations of the ER stacks with mitochondria. The associations have two components: a single, close ER-mitochondria contact on one side to the stack, and multiple layers of ER cisternae decorated by IP3Rs receptors on the side away from the mitochondria. Due to their location in the stacks, IP3Rs are never in contact with the mitochondria, although they are in their vicinity. We conclude that transfer of Ca2+ between ER and mitochondria is not directly mediated by IP3Rs, but is based on mitochondrial Ca2+ uptake from the local cytoplasmic spikes during IP3Rs’ activity.


Pozzan T, Rizzuto R, Volpe P, Meldolesi J. Molecular and cellular physiology of intracellular calcium stores. Physiol Rev. 1994 Jul;74(3):595-636. DOI: https://doi.org/10.1152/physrev.1994.74.3.595

Mikoshiba K, Furuichi T, Miyawaki A. Structure and function of IP3 receptors. Semin Cell Biol. 1994 Aug;5(4):273-81. DOI: https://doi.org/10.1006/scel.1994.1033

Berridge MJ. The endoplasmic reticulum: a multifunctional signaling organelle. Cell Calcium. 2002 Nov-Dec;32(5-6):235-49. DOI: https://doi.org/10.1016/S0143416002001823

Mikoshiba K. IP3 receptor/Ca2+ channel: from discovery to new signaling concepts. J Neurochem. 2007 Sep;102(5):1426-1446. DOI: https://doi.org/10.1111/j.1471-4159.2007.04825.x

Baker MR, Fan G, Serysheva II. Structure of IP3R channel: high-resolution insights from cryo-EM. Curr Opin Struct Biol. 2017 Oct;46:38-47. Epub 2017 Jun 12. DOI: https://doi.org/10.1016/j.sbi.2017.05.014

Franzini-Armstrong C, Protasi F. Ryanodine receptors of striated muscles: a complex channel capable of multiple interactions. Physiol Rev. 1997 Jul;77(3):699-729. DOI: https://doi.org/10.1152/physrev.1997.77.3.699

Rizzuto R, Bastianutto C, Brini M, Murgia M, Pozzan T. Mitochondrial Ca2+ homeostasis in intact cells. J Cell Biol. 1994 Sep;126(5):1183-94. DOI: https://doi.org/10.1083/jcb.126.5.1183

Rizzuto R, Simpson AW, Brini M, Pozzan T. Rapid changes of mitochondrial Ca2+ revealed by specifically targeted recombinant aequorin. Nature. 1992 Jul 23;358(6384):325-7. Erratum in: Nature 1992 Dec 24-31;360(6406):768. DOI: https://doi.org/10.1038/358325a0

Hajnóczky G, Robb-Gaspers LD, Seitz MB, Thomas AP. Decoding of cytosolic calcium oscillations in the mitochondria. Cell. 1995 Aug 11;82(3):415-24. DOI: https://doi.org/10.1016/0092-8674(95)90430-1

Rudolf R, Mongillo M, Magalhães PJ, Pozzan T. In vivo monitoring of Ca(2+) uptake into mitochondria of mouse skeletal muscle during contraction. J Cell Biol. 2004 Aug 16;166(4):527-36. DOI: https://doi.org/10.1083/jcb.200403102

Gillis JM. Inhibition of mitochondrial calcium uptake slows down relaxation in mitochondria-rich skeletal muscles. J Muscle Res Cell Motil. 1997 Aug;18(4):473-83.

izzuto R, Brini M, Murgia M, Pozzan T. Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria. Science. 1993 Oct 29;262(5134):744-7. DOI: https://doi.org/10.1126/science.8235595

Csordás G, Weaver D, Hajnóczky G. Endoplasmic Reticulum-Mitochondrial Contactology: Structure and Signaling Functions. Trends Cell Biol. 2018 Jul;28(7):523-540. Epub 2018 Mar 24. DOI: https://doi.org/10.1016/j.tcb.2018.02.009

Csordás G, Renken C, Várnai P, Walter L, Weaver D, Buttle KF, Balla T, Mannella CA, Hajnóczky G. Structural and functional features and significance of the physical linkage between ER and mitochondria. J Cell Biol. 2006 Sep 25;174(7):915-21. Epub 2006 Sep 18. DOI: https://doi.org/10.1083/jcb.200604016

Sharma VK, Ramesh V, Franzini-Armstrong C, Sheu SS. Transport of Ca2+ from sarcoplasmic reticulum to mitochondria in rat ventricular myocytes. J Bioenerg Biomembr. 2000 Feb;32(1):97-104. DOI: https://doi.org/10.1023/A:1005520714221

Boncompagni S, Pozzer D, Viscomi C, Ferreiro A, Zito E. Physical and Functional Cross Talk Between Endo-Sarcoplasmic Reticulum and Mitochondria in Skeletal Muscle. Antioxid Redox Signal. 2020 Apr 20;32(12):873-883. Epub 2019 Dec 11. DOI: https://doi.org/10.1089/ars.2019.7934

Hayashi T, Rizzuto R, Hajnoczky G, Su TP. MAM: more than just a housekeeper. Trends Cell Biol. 2009 Feb;19(2):81-8. Epub 2009 Jan 12. DOI: https://doi.org/10.1016/j.tcb.2008.12.002

Franzini-Armstrong C, Boncompagni S. The evolution of the mitochondria-to-calcium release units relationship in vertebrate skeletal muscles. J Biomed Biotechnol. 2011;2011:830573. Epub 2011 Oct 13. DOI: https://doi.org/10.1155/2011/830573

Katayama E, Funahashi H, Michikawa T, Shiraishi T, Ikemoto T, Iino M, Mikoshiba K. Native structure and arrangement of inositol-1,4,5-trisphosphate receptor molecules in bovine cerebellar Purkinje cells as studied by quick-freeze deep-etch electron microscopy. EMBO J. 1996 Sep 16;15(18):4844-51. Erratum in: EMBO J 1996 Dec 16;15(24):7188. DOI: https://doi.org/10.1002/j.1460-2075.1996.tb00865.x

Paolini C, Protasi F, Franzini-Armstrong C. The relative position of RyR feet and DHPR tetrads in skeletal muscle. J Mol Biol. 2004 Sep 3;342(1):145-53. DOI: https://doi.org/10.1016/j.jmb.2004.07.035

Khodakhah K, Armstrong CM. Induction of long-term depression and rebound potentiation by inositol trisphosphate in cerebellar Purkinje neurons. Proc Natl Acad Sci U S A. 1997 Dec 9;94(25):14009-14. DOI: https://doi.org/10.1073/pnas.94.25.14009

Lavorato M, Franzini-Armstrong C. Practical solutions to frequent problems encountered in thin section electron microscopy. Microscopy Today. 2017; May: 1-5. DOI: https://doi.org/10.1017/S1551929517000438

Satoh T, Ross CA, Villa A, Supattapone S, Pozzan T, Snyder SH, Meldolesi J. The inositol 1,4,5,-trisphosphate receptor in cerebellar Purkinje cells: quantitative immunogold labeling reveals concentration in an ER subcompartment. J Cell Biol. 1990 Aug;111(2):615-24. DOI: https://doi.org/10.1083/jcb.111.2.615

Boncompagni S, Rossi AE, Micaroni M, Beznoussenko GV, Polishchuk RS, Dirksen RT, Protasi F. Mitochondria are linked to calcium stores in striated muscle by developmentally regulated tethering structures. Mol Biol Cell. 2009 Feb;20(3):1058-67. Epub 2008 Nov 26. DOI: https://doi.org/10.1091/mbc.e08-07-0783

Pinton P, Giorgi C, Siviero R, Zecchini E, Rizzuto R. Calcium and apoptosis: ER-mitochondria Ca2+ transfer in the control of apoptosis. Oncogene. 2008 Oct 27;27(50):6407-18. DOI: https://doi.org/10.1038/onc.2008.308

Scorrano L, De Matteis MA, Emr S, Giordano F, Hajnóczky G, Kornmann B, Lackner LL, Levine TP, Pellegrini L, Reinisch K, Rizzuto R, Simmen T, Stenmark H, Ungermann C, Schuldiner M. Coming together to define membrane contact sites. Nat Commun. 2019 Mar 20;10(1):1287. DOI: https://doi.org/10.1038/s41467-019-09253-3

Rizzuto R, Pinton P, Carrington W, Fay FS, Fogarty KE, Lifshitz LM, Tuft RA, Pozzan T. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science. 1998 Jun 12;280(5370):1763-6. DOI: https://doi.org/10.1126/science.280.5370.1763

Rizzuto R, Pozzan T. Microdomains of intracellular Ca2+: molecular determinants and functional consequences. Physiol Rev. 2006 Jan;86(1):369-408. DOI: https://doi.org/10.1152/physrev.00004.2005

Rizzuto R, Brini M, Murgia M, Pozzan T. Microdomains with high Ca2+ close to IP3-sensitive channels that are sensed by neighboring mitochondria. Science. 1993 Oct 29;262(5134):744-7. DOI: https://doi.org/10.1126/science.8235595

Taylor CW, Tovey SC, Rossi AM, Lopez Sanjurjo CI, Prole DL, Rahman T. Structural organization of signalling to and from IP3 receptors. Biochem Soc Trans. 2014 Feb;42(1):63-70. DOI: https://doi.org/10.1042/BST20130205

Fierro L, DiPolo R, Llano I. Intracellular calcium clearance in Purkinje cell somata from rat cerebellar slices. J Physiol. 1998 Jul 15;510 ( Pt 2)(Pt 2):499-512. DOI: https://doi.org/10.1111/j.1469-7793.1998.499bk.x

Gomez LC, Kawaguchi SY, Collin T, Jalil A, Gomez MDP, Nasi E, Marty A, Llano I. Influence of spatially segregated IP3-producing pathways on spike generation and transmitter release in Purkinje cell axons. Proc Natl Acad Sci U S A. 2020 May 19;117(20):11097-11108. Epub 2020 May 1. Erratum in: Proc Natl Acad Sci U S A. 2020 Jun 9;117(23):13176. DOI: https://doi.org/10.1073/pnas.2000148117

Tinel H, Cancela JM, Mogami H, Gerasimenko JV, Gerasimenko OV, Tepikin AV, Petersen OH. Active mitochondria surrounding the pancreatic acinar granule region prevent spreading of inositol trisphosphate-evoked local cytosolic Ca(2+) signals. EMBO J. 1999 Sep 15;18(18):4999-5008. DOI: https://doi.org/10.1093/emboj/18.18.4999

Iyer, R., & Franzini-Armstrong, C. (2021). The location of InsP3 receptors in Purkinje cells of murine cerebellum does not supports a direct interaction in the transfer of calcium ions between ER and mitochondria. European Journal of Translational Myology, 31(3). https://doi.org/10.4081/ejtm.2021.9935

Downloads

Download data is not yet available.

Citations