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Identification of the ankyrin-binding domain of the mouse T-lymphoma cell inositol 1,4,5-trisphosphate (IP3) receptor and its role in the regulation of IP3-mediated internal Ca2+ release.

Abstract
In this study we have used several complementary techniques to explore the interaction between the membrane linker molecule, ankyrin, and the inositol 1,4,5-trisphosphate (IP3) receptor in mouse T-lymphoma cells. Using double immunolabeling and laser confocal microscopy, we have found that both cytoplasmic IP3 receptor and ankyrin are preferentially accumulated within ligand-induced lymphocyte receptor-capped structures. The binding between ankyrin and IP3 receptor appears to be very specific. Further analyses indicate that the amino acid sequence GGVGDVLRKPS in the IP3 receptor shares a great deal of structural homology with the ankyrin-binding domain located in certain well characterized ankyrin-binding proteins such as the cell adhesion molecule, CD44. Biochemical studies using competition binding assays and a synthetic peptide identical to GGVGDVLRKPS (a sequence detected in rat brain IP3 receptor (amino acids 2548-2558) and mouse brain IP3 receptor (amino acids 2546-2556)) indicate that this 11-amino acid peptide binds specifically to ankyrin (but not fodrin or spectrin). Furthermore, this peptide competes effectively for ankyrin binding to IP3 receptor-containing vesicles and/or purified IP3 receptor, and it blocks ankyrin-induced inhibitory effects on IP3 binding and IP3-mediated internal Ca2+ release in mouse T-lymphoma cells. These findings suggest that this amino acid sequence, GGVGDVLRKPS, which is located close to the C terminus of the IP3 receptor, resides on the cytoplasmic side (not the luminal side) of IP3 receptor-containing vesicles. This unique region appears to be an important part of the IP3 receptor ankyrin-binding domain and may play an important role in the regulation of IP3 receptor-mediated internal Ca2+ release during lymphocyte activation.
AuthorsL Y Bourguignon, H Jin
JournalThe Journal of biological chemistry (J Biol Chem) Vol. 270 Issue 13 Pg. 7257-60 (Mar 31 1995) ISSN: 0021-9258 [Print] United States
PMID7706265 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Ankyrins
  • Calcium Channels
  • Cytoskeletal Proteins
  • Inositol 1,4,5-Trisphosphate Receptors
  • Iodine Radioisotopes
  • Receptors, Cytoplasmic and Nuclear
  • Inositol 1,4,5-Trisphosphate
  • Calcium
Topics
  • Amino Acid Sequence
  • Animals
  • Ankyrins (metabolism)
  • Binding Sites
  • Brain (metabolism)
  • Calcium (metabolism)
  • Calcium Channels (chemistry, isolation & purification, metabolism)
  • Cell Line
  • Cytoskeletal Proteins (metabolism)
  • Fluorescent Antibody Technique
  • Inositol 1,4,5-Trisphosphate (pharmacology)
  • Inositol 1,4,5-Trisphosphate Receptors
  • Iodine Radioisotopes
  • Kinetics
  • Lymphoma, T-Cell (metabolism)
  • Mice
  • Molecular Sequence Data
  • Radioligand Assay
  • Rats
  • Receptors, Cytoplasmic and Nuclear (chemistry, isolation & purification, metabolism)

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