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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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Notch signaling and the various Notch receptors used in this paper. (A) The SuH/Nintra signaling pathway. (B) The structures of Notch receptors used in this paper; relative activities shown on an arbitrary scale. TM, transmembrane domain.
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fig1: Notch signaling and the various Notch receptors used in this paper. (A) The SuH/Nintra signaling pathway. (B) The structures of Notch receptors used in this paper; relative activities shown on an arbitrary scale. TM, transmembrane domain.

Mentions: When Dl on one cell binds N on the other, N gets proteolytically cleaved, first by the Kuzbanian or TACE metalloproteases (S2 cleavage) and subsequently by the Presenilin (Psn)/γ-secretase complex (S3 cleavage). The Notch intracellular domain (Nintra) is released from the plasma membrane, translocated to the nucleus, and in association with the transcription factor Suppressor of Hairless (SuH) activates transcription of target genes such as the Enhancer of split Complex (E(spl)C) genes (see Fig. 1 A). One group of cells accumulates a high level of N activity to become one cell type, whereas the other group accumulates very little or none to become the other cell type (Artavanis-Tsakonas et al., 1999; Brou et al., 2000; Mumm and Kopan, 2000; Lieber et al., 2002). From here onwards, N activity dependent on SuH and Nintra will be referred to as the SuH/Nintra signaling. Dl also gets cleaved in a manner similar to N; its consequence is not clear but is thought to down-regulate N signaling (Qi et al., 1999; Mishra-Gorur et al., 2002; Bland et al., 2003; Ikeuchi and Sisodia, 2003; LaVoie and Selkoe, 2003).


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)

Notch signaling and the various Notch receptors used in this paper. (A) The SuH/Nintra signaling pathway. (B) The structures of Notch receptors used in this paper; relative activities shown on an arbitrary scale. TM, transmembrane domain.
© Copyright Policy
Related In: Results  -  Collection

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

fig1: Notch signaling and the various Notch receptors used in this paper. (A) The SuH/Nintra signaling pathway. (B) The structures of Notch receptors used in this paper; relative activities shown on an arbitrary scale. TM, transmembrane domain.
Mentions: When Dl on one cell binds N on the other, N gets proteolytically cleaved, first by the Kuzbanian or TACE metalloproteases (S2 cleavage) and subsequently by the Presenilin (Psn)/γ-secretase complex (S3 cleavage). The Notch intracellular domain (Nintra) is released from the plasma membrane, translocated to the nucleus, and in association with the transcription factor Suppressor of Hairless (SuH) activates transcription of target genes such as the Enhancer of split Complex (E(spl)C) genes (see Fig. 1 A). One group of cells accumulates a high level of N activity to become one cell type, whereas the other group accumulates very little or none to become the other cell type (Artavanis-Tsakonas et al., 1999; Brou et al., 2000; Mumm and Kopan, 2000; Lieber et al., 2002). From here onwards, N activity dependent on SuH and Nintra will be referred to as the SuH/Nintra signaling. Dl also gets cleaved in a manner similar to N; its consequence is not clear but is thought to down-regulate N signaling (Qi et al., 1999; Mishra-Gorur et al., 2002; Bland et al., 2003; Ikeuchi and Sisodia, 2003; LaVoie and Selkoe, 2003).

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