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The adhesion force of Notch with Delta and the rate of Notch signaling.

Ahimou F, Mok LP, Bardot B, Wesley C - J. Cell Biol. (2004)

Bottom Line: Notch signaling is repeatedly used during animal development to specify cell fates.Reduced turnover or Delta pulling accelerate this loss.These data suggest that strong adhesion between Notch and Delta might serve as a booster for initiating Notch signaling at a high rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Genetics, The University of Vermont, VT 05405, USA.

ABSTRACT
Notch signaling is repeatedly used during animal development to specify cell fates. Using atomic force microscopy on live cells, chemical inhibitors, and conventional analyses, we show that the rate of Notch signaling is linked to the adhesion force between cells expressing Notch receptors and Delta ligand. Both the Notch extracellular and intracellular domains are required for the high adhesion force with Delta. This high adhesion force is lost within minutes, primarily due to the action of Presenilin on Notch. Reduced turnover or Delta pulling accelerate this loss. These data suggest that strong adhesion between Notch and Delta might serve as a booster for initiating Notch signaling at a high rate.

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Chloroquine accelerates the loss of detachment force between Notch receptors and Dl. (A) Detachment forces between the S2-Dl cantilevers and chloroquine-pretreated S2 cells expressing Notch receptors, in 1× PBS+Ca2+. (B) A Western blot showing the levels of N molecules, in chloroquine-pretreated or untreated S2-N cells, in the presence of S2 or S2-Dl cells.
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fig7: Chloroquine accelerates the loss of detachment force between Notch receptors and Dl. (A) Detachment forces between the S2-Dl cantilevers and chloroquine-pretreated S2 cells expressing Notch receptors, in 1× PBS+Ca2+. (B) A Western blot showing the levels of N molecules, in chloroquine-pretreated or untreated S2-N cells, in the presence of S2 or S2-Dl cells.

Mentions: S2 and S3 fragments are produced at low levels in S2-N cells, and N levels in these cells turn over even in the absence of S2-Dl cells (unpublished data), suggesting a connection between the turnover rate and N signaling. Therefore, we used chloroquine to block turnover in S2 cells expressing the various Notch receptors and measured the detachment force between them and the S2-Dl cantilevers. We found that the decrease in detachment force was accelerated (Fig. 7 A). Western blot analysis showed that chloroquine treatment of S2-N cells resulted in accumulation of the S3 cleaved fragment even in the absence of Dl (Fig. 7 B; 7.8 ± 0.96, P < 0.05; n = 3). We also examined the level of E(spl)C m3 expression and found that it was increased in chloroquine-treated samples (unpublished data). Thus, it appeared that blocking N turnover advanced the rate of S3 cleavage and SuH/Nintra signaling, thereby accelerating the rate of decrease in the detachment force after Dl binding.


The adhesion force of Notch with Delta and the rate of Notch signaling.

Ahimou F, Mok LP, Bardot B, Wesley C - J. Cell Biol. (2004)

Chloroquine accelerates the loss of detachment force between Notch receptors and Dl. (A) Detachment forces between the S2-Dl cantilevers and chloroquine-pretreated S2 cells expressing Notch receptors, in 1× PBS+Ca2+. (B) A Western blot showing the levels of N molecules, in chloroquine-pretreated or untreated S2-N cells, in the presence of S2 or S2-Dl cells.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2172611&req=5

fig7: Chloroquine accelerates the loss of detachment force between Notch receptors and Dl. (A) Detachment forces between the S2-Dl cantilevers and chloroquine-pretreated S2 cells expressing Notch receptors, in 1× PBS+Ca2+. (B) A Western blot showing the levels of N molecules, in chloroquine-pretreated or untreated S2-N cells, in the presence of S2 or S2-Dl cells.
Mentions: S2 and S3 fragments are produced at low levels in S2-N cells, and N levels in these cells turn over even in the absence of S2-Dl cells (unpublished data), suggesting a connection between the turnover rate and N signaling. Therefore, we used chloroquine to block turnover in S2 cells expressing the various Notch receptors and measured the detachment force between them and the S2-Dl cantilevers. We found that the decrease in detachment force was accelerated (Fig. 7 A). Western blot analysis showed that chloroquine treatment of S2-N cells resulted in accumulation of the S3 cleaved fragment even in the absence of Dl (Fig. 7 B; 7.8 ± 0.96, P < 0.05; n = 3). We also examined the level of E(spl)C m3 expression and found that it was increased in chloroquine-treated samples (unpublished data). Thus, it appeared that blocking N turnover advanced the rate of S3 cleavage and SuH/Nintra signaling, thereby accelerating the rate of decrease in the detachment force after Dl binding.

Bottom Line: Notch signaling is repeatedly used during animal development to specify cell fates.Reduced turnover or Delta pulling accelerate this loss.These data suggest that strong adhesion between Notch and Delta might serve as a booster for initiating Notch signaling at a high rate.

View Article: PubMed Central - PubMed

Affiliation: Department of Microbiology and Molecular Genetics, The University of Vermont, VT 05405, USA.

ABSTRACT
Notch signaling is repeatedly used during animal development to specify cell fates. Using atomic force microscopy on live cells, chemical inhibitors, and conventional analyses, we show that the rate of Notch signaling is linked to the adhesion force between cells expressing Notch receptors and Delta ligand. Both the Notch extracellular and intracellular domains are required for the high adhesion force with Delta. This high adhesion force is lost within minutes, primarily due to the action of Presenilin on Notch. Reduced turnover or Delta pulling accelerate this loss. These data suggest that strong adhesion between Notch and Delta might serve as a booster for initiating Notch signaling at a high rate.

Show MeSH
Related in: MedlinePlus