DOI: 10.1085/jgp.114.2.243. Location of the Permeation Pathway in the Recombinant Type 1 Inositol 1,4,5-Trisphosphate Receptor

Location of the Permeation Pathway in the Recombinant Type 1 Inositol 1,4,5-Trisphosphate Receptor

10.1085/jgp.114.2.243

Crossref journal-article

Rockefeller University Press

The Journal of General Physiology (291)

Abstract

The inositol 1,4,5-trisphosphate receptor (InsP3R) forms ligand-regulated intracellular Ca2+ release channels in the endoplasmic reticulum of all mammalian cells. The InsP3R has been suggested to have six transmembrane regions (TMRs) near its carboxyl terminus. A TMR-deletion mutation strategy was applied to define the location of the InsP3R pore. Mutant InsP3Rs were expressed in COS-1 cells and single channel function was defined in planar lipid bilayers. Mutants having the fifth and sixth TMR (and the interceding lumenal loop), but missing all other TMRs, formed channels with permeation properties similar to wild-type channels (gCs = 284; gCa = 60 pS; PCa/PCs = 6.3). These mutant channels bound InsP3, but ligand occupancy did not regulate the constitutively open pore (Po &gt; 0.80). We propose that a region of 191 amino acids (including the fifth and sixth TMR, residues 2398–2589) near the COOH terminus of the protein forms the InsP3R pore. Further, we have produced a constitutively open InsP3R pore mutant that is ideal for future site-directed mutagenesis studies of the structure–function relationships that define Ca2+ permeation through the InsP3R channel.

Bibliography

Ramos-Franco, J., Galvan, D., Mignery, G. A., & Fill, M. (1999). Location of the Permeation Pathway in the Recombinant Type 1 Inositol 1,4,5-Trisphosphate Receptor. The Journal of General Physiology, 114(2), 243â250.

Authors 4

Josefina Ramos-Franco (first)
Daniel Galvan (additional)
Gregory A. Mignery (additional)
Michael Fill (additional)

References 28 Referenced 66

{'key': '2023072918094500300_Baudetetal1994', 'first-page': '9', 'article-title': 'How to make and use calcium-specific mini- and microelectrodes', 'volume': '40', 'author': 'Baudet', 'year': '1994', 'journal-title': 'Methods Cell Biol.'} / Methods Cell Biol. / How to make and use calcium-specific mini- and microelectrodes by Baudet (1994)
10.1073/pnas.96.7.3345 / Proc. Natl. Acad. Sci. USA / Luminal loop of the ryanodine receptora pore-forming segment? by Balshaw (1999)
10.1038/351751a0 / Nature. / Bell-shaped calcium-response curves of Ins(1,4,5)P3 and calcium-gated channels from endoplasmic reticulum of cerebellum by Bezprozvanny (1991)
10.1016/B978-0-12-550640-3.50038-1 / In Handbook of Membrane Channels / InsP3 receptorfunctional properties and regulation by Bezprozvanny (1994)
10.1007/BF00232713 / J. Membr. Biol / The inositol 1,4,5-trisphosphate (InsP3) receptor by Bezprozvanny (1995)
10.1042/bj3220575 / Biochem. J. / Isoform diversity of the inositol 1,4,5-trisphosphate receptor in cell types of mouse origin by De Smedt (1997)
{'key': '2023072918094500300_Gaoetal1999', 'first-page': 'A303', 'article-title': 'Mutation of charged amino acids in a putative lumenal loop of the skeletal muscle Ca2+ release channel results in the loss of high affinity ryanodine binding', 'volume': '76', 'author': 'Gao', 'year': '1999', 'journal-title': 'Biophys. J.'} / Biophys. J. / Mutation of charged amino acids in a putative lumenal loop of the skeletal muscle Ca2+ release channel results in the loss of high affinity ryanodine binding by Gao (1999)
{'key': '2023072918094500300_Gorman1985'}
10.1038/23954 / Nature. / Type-III InsP3 receptor channel stays open in the presence of increased calcium by Hagar (1998)
10.1016/0898-6568(95)02012-8 / Cell Signal / The inositol trisphosphate receptor family by Joseph (1996)
10.1074/jbc.272.3.1579 / J.Biol.Chem / Membrane insertion, glycosylation, and oligomerization of inositol trisphosphate receptors in a cell-free translation system by Joseph (1997)
10.1085/jgp.111.6.847 / J. Gen. Physiol. / Single channel properties of inositol trisphosphate receptor heterologously expressed in HEK-293 cells by Kaznacheyeva (1998)
10.1038/297498a0 / Nature. / Reversal of current through Ca2+ channels in dialyzed single heart cells by Lee (1982)
10.1073/pnas.96.7.4164 / Proc. Natl. Acad. Sci. USA. / A mutation in the transmembrane/lumenal domain of the ryanodine receptor is associated with abnormal Ca2+ release channel function and severe central core disease by Lynch (1999)
10.1016/S0021-9258(17)37092-8 / J. Biol. Chem. / Transmembrane topology and sites of glycosylation of the inositol trisphosphate receptor by Michikawa (1994)
10.1038/342192a0 / Nature. / Putative receptor for inositol 1,4,5-trisphosphate similar to ryanodine receptor by Mignery (1989)
10.1002/j.1460-2075.1990.tb07609.x / EMBO (Eur. Mol. Biol. Organ.) J. / The ligand-binding site and transduction mechanism in the inositol-1,4,5-trisphosphate receptor by Mignery (1990)
10.1016/S0021-9258(19)38397-8 / J. Biol. Chem / Structure and expression of the rat inositol-1,4,5-trisphosphate receptor by Mignery (1990)
10.1016/B978-0-12-185285-6.50028-2 / Methods Neurosci. / Molecular analysis of inositol 1,4,5-trisphosphate receptors by Mignery (1993)
10.1007/s004410050641 / Cell Tissue Res. / Immunohistochemical localization of inositol 1,4,5-trisphosphate receptors in non-neural tissues, with special reference to epithelia, the reproductive system and muscular tissues by Nakanishi (1996)
10.1016/S0021-9258(19)61949-6 / J. Biol. Chem / Co-expression in vertebrate tissues and cell lines of multiple inositol 1,4,5-trisphosphate (InsP3) receptors with distinct affinities for InsP3 by Newton (1994)
10.1074/jbc.272.38.23961 / J. Biol. Chem / Identification and functional reconstitution of the type-2 InsP3 receptor from ventricular cardiac myocytes by Perez (1997)
10.1016/S0006-3495(98)77572-1 / Biophys. J. / Isoform specific function of single inositol 1,4,5-trisphosphate receptor channels by Ramos-Franco (1998)
10.1016/S0006-3495(98)77721-5 / Biophys. J. / Single channel function of recombinant type-1 inositol 1,4,5-trisphosphate receptor ligand binding domain splice variants by Ramos-Franco (1998)
10.1042/bj3230273 / Biochem. J. / Intracellular targeting and homotetramer targeting of a truncated inositol 1,4,5-trisphosphate receptor-green fluorescent protein chimera in Xenopus laevis oocytesevidence for the involvement of the membrane spanning domain in endoplasmic reticulum targeting and homotetramer complex formation by Sayers (1997)
10.1074/jbc.271.10.5941 / J. Biol. Chem / A leucine zipper stabilizes the pentameric membrane domain of phospholamban and forms a coiled-coil pore structure by Simmerman (1996)
10.1002/j.1460-2075.1991.tb04882.x / EMBO (Eur. Mol. Biol. Organ.) J. / The structure of a novel InsP3 receptor by Südhof (1991)
10.1085/jgp.100.3.479 / J. Gen. Physiol / Divalent cation conduction in the ryanodine receptor of sheep cardiac muscle sarcoplasmic reticulum by Tinker (1992)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:50 p.m.)
Deposited	2 years, 1 month ago (July 29, 2023, 2:10 p.m.)
Indexed	11 months, 3 weeks ago (Sept. 6, 2024, 7:57 p.m.)
Issued	26 years ago (Aug. 1, 1999)
Published	26 years ago (Aug. 1, 1999)
Published Online	26 years ago (Aug. 1, 1999)
Published Print	26 years ago (Aug. 1, 1999)

Funders 0

None

BibTeX

@article{Ramos_Franco_1999, title={Location of the Permeation Pathway in the Recombinant Type 1 Inositol 1,4,5-Trisphosphate Receptor}, volume={114}, ISSN={1540-7748}, url={http://dx.doi.org/10.1085/jgp.114.2.243}, DOI={10.1085/jgp.114.2.243}, number={2}, journal={The Journal of General Physiology}, publisher={Rockefeller University Press}, author={Ramos-Franco, Josefina and Galvan, Daniel and Mignery, Gregory A. and Fill, Michael}, year={1999}, month=aug, pages={243–250} }

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      "URL": "https://rupress.org/jgp/article/114/2/243/43792/Location-of-the-Permeation-Pathway-in-the"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1999,
        8,
        1
      ]
    ]
  },
  "references-count": 28,
  "journal-issue": {
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    "published-print": {
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  },
  "URL": "http://dx.doi.org/10.1085/jgp.114.2.243",
  "relation": {},
  "ISSN": [
    "0022-1295",
    "1540-7748"
  ],
  "subject": [],
  "published": {
    "date-parts": [
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        1999,
        8,
        1
      ]
    ]
  }
}