Agonist-induced down-regulation of type 1 and type 3 inositol 1,4,5-tris-phosphate receptors in A7r5 and DDT1 MF-2 smooth muscle cells

Sipma, Henk; Deelman, Leo E.; Smedt, Humbert De; Missiaen, Ludwig; Parys, Jan B.; Vanlingen, Sara; Henning, Robert H.; Casteels, Rik

doi:10.1016/s0143-4160(98)90070-7

Cited by 50 publications

(57 citation statements)

References 44 publications

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“…Furthermore, region 316-352 is not compatible with known degradation signals ; this sequence is highly hydrophilic [5], whereas degradation signals are often stretches of hydrophobic residues [31,35]. In addition, as all three Ins(1,4,5)P $ Rs are ubiquitinated in response to phosphoinositidase C activation [17][18][19][20], it would be expected that the 316-352 region would be highly conserved between receptors if it were the degradation signal. This, however, is not so : the 316-352 region is poorly conserved in types I, II and III receptors (only 16 % similarity in this region).…”

Section: Discussionmentioning

confidence: 99%

“…Persistent phosphoinositidase C activation can cause Ins(1,4,5)P $ R down-regulation [12][13][14][15][16][17][18] ; Ins(1,4,5)P $ Rs therefore represent a novel locus for the desensitization of phosphoinositidase C-mediated signalling. This down-regulation decreases the sensitivity of Ca# + stores to Ins(1,4,5)P $ [12,18], is due to accelerated receptor proteolysis [14,15], has a half-time of 0.5-2 h [14][15][16][17][18], can decrease Ins(1,4,5)P $ R levels by as much as 90 % [14,15], is evident with all three receptor types [15,17,18], and occurs in a variety of cells in itro [14][15][16][17][18] and in i o [19].…”

Section: Ins(145)pmentioning

confidence: 99%

“…This down-regulation decreases the sensitivity of Ca# + stores to Ins(1,4,5)P $ [12,18], is due to accelerated receptor proteolysis [14,15], has a half-time of 0.5-2 h [14][15][16][17][18], can decrease Ins(1,4,5)P $ R levels by as much as 90 % [14,15], is evident with all three receptor types [15,17,18], and occurs in a variety of cells in itro [14][15][16][17][18] and in i o [19]. Although the mechanism of Ins(1,4,5)P $ R proteolysis has yet to be defined, it might be executed through the ubiquitin\ proteasome pathway [17][18][19][20], a pathway crucial to basal and regulated degradation of many cytosolic, nuclear, and membrane proteins [21][22][23][24][25].…”

Section: Ins(145)pmentioning

confidence: 99%

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Ligand binding directly stimulates ubiquitination of the inositol 1,4,5-trisphosphate receptor

Zhu

Wojcikiewicz

2000

Biochemical Journal

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Down-regulation of the Ins(1,4,5)P3 receptor is an adaptive response to the activation of certain phosphoinositidase C-linked cell-surface receptors. It is manifested as a profound decline in cellular Ins(1,4,5)P3 receptor content, occurs with a half-time of 0.5-2 h and is due to accelerated proteolysis. It has been shown that this process is mediated by the ubiquitin/proteasome pathway and is therefore initiated by Ins(1,4,5)P3 receptor ubiquitination. To investigate the role of ligand binding in Ins(1,4,5)P3 receptor ubiquitination, we expressed ‘exogenous’ wild-type and ligand-binding-defective mutant type I Ins(1,4,5)P3 receptors in human neuroblastoma SH-SY5Y cells, in which muscarinic receptor activation elicits Ins(1,4,5)P3 receptor down-regulation. We found (1) that exogenous wild-type Ins(1,4,5)P3 receptors are efficiently ubiquitinated in response to muscarinic receptor stimulation, (2) that exogenous ligand binding-defective mutant Ins(1,4,5)P3 receptors are resistant to ubiquitination, (3) that this resistance is not caused by the removal of potential ubiquitin-conjugating sites in the mutated region, and (4) that in heterotetramers of exogenous mutant receptors and ‘endogenous’ receptors, only the latter are targeted for ubiquitination. These results indicate that the binding of Ins(1,4,5)P3 directly stimulates ubiquitination of the Ins(1,4,5)P3 receptor and that the targeting of Ins(1,4,5)P3 receptors for ubiquitination is a highly specific process. We therefore propose that an Ins(1,4,5)P3-binding-induced conformational change in the receptor exposes a degradation signal that leads to ubiquitination.

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Section: Discussionmentioning

confidence: 99%

Section: Ins(145)pmentioning

confidence: 99%

Section: Ins(145)pmentioning

confidence: 99%

See 1 more Smart Citation

Ligand binding directly stimulates ubiquitination of the inositol 1,4,5-trisphosphate receptor

Zhu

Wojcikiewicz

2000

Biochemical Journal

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Section: Introductionmentioning

confidence: 99%

“…Indeed, there is now substantial evidence that chronic activation of such cell-surface receptors can lead to a marked down-regulation of types 1 and 3 InsP $ Rs [13][14][15], and a consequent reduction in the ability of InsP $ to mobilize Ca# + . It has also been suggested that this could represent a mechanism of heterologous desensitization for Ca# + -mobilizing agonists [13,15]. Furthermore, there is evidence that type 1 InsP $ R is progressively increased by retinoic acid-induced cellular differentiation of HL-60 cells [16], and a dramatic elevation of type 3 InsP $ Rs appears to accompany apoptosis in concentration ; PTX, pertussis toxin ; Tg, thapsigargin ; SERCA, sarco-/endo-plasmic-reticular Ca 2 + -ATPase ; fura-2/AM, fura-2 acetoxymethyl ester ; 2MeS-ATP, 2-methylthio-ATP.…”

Section: Introductionmentioning

confidence: 99%

Enhanced purinoceptor-mediated Ca2+ signalling in L-fibroblasts overexpressing type 1 inositol 1,4,5-trisphosphate receptors

Davis

Challiss

Nahorski

1999

Biochemical Journal

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Mouse L-fibroblast cells stably transfected with either type 1 Ins(1,4,5)P $ receptor (InsP $ R) cDNA (L15) or the vector control (Lvec) have been used to investigate the functional consequences of increased InsP $ R density on receptor-mediated Ca# + signalling. L15 cells express approx. 8-fold higher levels of the type 1 InsP $ R compared with Lvec cells, which endogenously express essentially only the type 1 InsP $ R protein. Stimulation of Lvec and L15 cells with UTP or ATP increased cytosolic Ca# + concentration to a greater extent in L15 cells at all agonist concentrations. UTP and ATP were equipotent, suggestive of the presence of endogenous cell-surface metabotropic P2Y # -purinoceptors. In both cell clones the purinoceptors were coupled via pertussis-toxin-insensitive Gprotein(s) to phospholipase C activation, resulting in similar concentration-dependent accumulations of InsP $ . Single-cell microfluorimetry revealed that overexpression of InsP $ Rs reduced the threshold for purinoceptor-mediated Ca# + signalling. L-

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Expression of Inositol 1,4,5-Trisphosphate Receptors in Mouse Oocytes and Early Embryos: The Type I Isoform Is Upregulated in Oocytes and Downregulated after Fertilization

Parrington

Brind

Smedt

et al. 1998

Developmental Biology

115

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A fertilization-induced increase in intracellular Ca2+ is responsible for initiating all of the events of egg activation. In mammals, the Ca2+ increase takes the form of a series of Ca2+ oscillations showing complex temporal and spatial properties. To understand the nature of these changes, we have investigated the expression patterns of the three isoforms of the inositol trisphosphate receptor (InsP3R) during oocyte maturation and preimplantation development. We find that mouse oocytes express mRNAs for all three InsP3R subtypes. Semiquantitative ratio reverse-transcriptase polymerase chain reaction shows that the type II isoform is the predominant message in mature oocytes, representing 67% of the InsP3R mRNA. In contrast, protein analysis reveals that the type I isoform accounts for all of the detectable InsP3R protein, despite representing only 20% of the InsP3R mRNA. The levels of InsP3R protein were examined to determine whether they correlated with the Ca2+ signaling events surrounding the fertilization process. Type I InsP3R protein increased during oocyte maturation and, in addition, within 8 h of fertilization underwent a dramatic decrease. During development to the blastocyst the level of type I InsP3R protein did not return to prefertilization levels and types II and III remained below our detection limit. The decrease in InsP3R protein after fertilization was found to correlate with a decrease in the sensitivity of InsP3-induced Ca2+ release. These studies show that the expression of InsP3R mRNA is developmentally regulated, that Ca2+ signaling at fertilization is mediated exclusively through the type I InsP3R, and that the InsP3R is downregulated after fertilization.

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Agonist-induced down-regulation of type 1 and type 3 inositol 1,4,5-tris-phosphate receptors in A7r5 and DDT1 MF-2 smooth muscle cells

Cited by 50 publications

References 44 publications

Ligand binding directly stimulates ubiquitination of the inositol 1,4,5-trisphosphate receptor

Ligand binding directly stimulates ubiquitination of the inositol 1,4,5-trisphosphate receptor

Enhanced purinoceptor-mediated Ca2+ signalling in L-fibroblasts overexpressing type 1 inositol 1,4,5-trisphosphate receptors

Expression of Inositol 1,4,5-Trisphosphate Receptors in Mouse Oocytes and Early Embryos: The Type I Isoform Is Upregulated in Oocytes and Downregulated after Fertilization

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