Junctate is a key element in calcium entry induced by activation of InsP3 receptors and/or calcium store depletion.
In many cell types agonist-receptor activation leads to a rapid and transient release of Ca(2+) from intracellular stores via activation of inositol 1,4,5 trisphosphate (InsP(3)) receptors (InsP(3)Rs). Stimulated cells activate store- or receptor-operated calcium channels localized in the plasma membrane, allowing entry of extracellular calcium into the cytoplasm, and thus replenishment of intracellular calcium stores. Calcium entry must be finely regulated in order to prevent an excessive intracellular calcium increase. Junctate, an integral calcium binding protein of endo(sarco)plasmic reticulum membrane, (a) induces and/or stabilizes peripheral couplings between the ER and the plasma membrane, and (b) forms a supramolecular complex with the InsP(3)R and the canonical transient receptor potential protein (TRPC) 3 calcium entry channel. The full-length protein modulates both agonist-induced and store depletion-induced calcium entry, whereas its NH(2) terminus affects receptor-activated calcium entry. RNA interference to deplete cells of endogenous junctate, knocked down both agonist-activated calcium release from intracellular stores and calcium entry via TRPC3. These results demonstrate that junctate is a new protein involved in calcium homeostasis in eukaryotic cells.
Department of Anesthesiology, University of Basel Kantosspital, Basel, Switzerland.
Susan
S
Treves
Clara
C
Franzini-Armstrong
Luca
L
Moccagatta
Christophe
C
Arnoult
Cristiano
C
Grasso
Adam
A
Schrum
Sylvie
S
Ducreux
Michael X
MX
Zhu
Katsuhiko
K
Mikoshiba
Thierry
T
Girard
Sophia
S
Smida-Rezgui
Michel
M
Ronjat
Francesco
F
Zorzato
D000818:Animals; D019556:COS Cells; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002412:Cations; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D004594:Electrophysiology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins; D006801:Humans; D015151:Immunoblotting; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008164:Luminescent Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000502:physiology*; D008854:Microscopy, Electron; D006899:Mixed Function Oxygenases / Q000502:physiology*; D009124:Muscle Proteins / Q000502:physiology*; D010455:Peptides / Q000737:chemistry; D011233:Precipitin Tests; D017434:Protein Structure, Tertiary; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000737:chemistry; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013347:Subcellular Fractions; D013997:Time Factors; D014162:Transfection; D010738:Type C Phospholipases / Q000378:metabolism
D015220:Calcium Channels; D002135:Calcium-Binding Proteins; D002412:Cations; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D008164:Luminescent Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; D010455:Peptides; D012330:RNA, Double-Stranded; D018160:Receptors, Cytoplasmic and Nuclear; D049452:Green Fluorescent Proteins; D006899:Mixed Function Oxygenases; C419389:ASPH protein, human; D010738:Type C Phospholipases; D002118:Calcium