Endocytosis-independent mechanisms of Delta ligand proteolysis

Delwig, Anton; Bland, Christin E.; Beem-Miller, Micah; Kimberly, Priscilla J.; Rand, Matthew D.

doi:10.1016/j.yexcr.2005.12.037

Cited by 21 publications

(37 citation statements)

References 57 publications

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“…It has been shown that incubation of Drosophila Delta-expressing S2 cells with Notch-expressing S2 cells caused a transient accumulation of C-terminal fragments of Delta that had been cleaved by latent proteases (13,15). We therefore investigated whether mouse Dll1 processing could also be induced through interaction with Notch.…”

Section: Resultsmentioning

confidence: 99%

“…It has been reported that Delta is cleaved sequentially by proteases, including ADAM and γ-secretase (8–11) and processing of Drosophila Delta was up-regulated in co-cultures with Notch-expressing S2 cells (13,15). It has also been reported that a truncated intracellular isoform of Delta shows prominent nuclear localization (10,11,13).…”

Section: Discussionmentioning

confidence: 99%

“…have reported that Drosophila Delta proteolysis differs from the conventional RIP, because TM processing of Drosophila Delta is not sensitive to preseniline, and TM and JM cleavages occur independently of each other. Based on these observations, they concluded that Delta proteolysis can act to modulate Delta activity (15). However, mouse and rat Delta like protein1 (Dll1) are sequentially processed and preseniline is essential for these proteolysis (10,11).…”

Section: Introductionmentioning

confidence: 99%

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The Delta intracellular domain mediates TGF-β/Activin signaling through binding to Smads and has an important bi-directional function in the Notch–Delta signaling pathway

Hiratochi

Nagase

Kuramochi

et al. 2007

Nucleic Acids Research

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Delta is a major transmembrane ligand for Notch receptor that mediates numerous cell fate decisions. The Notch signaling pathway has long been thought to be mono-directional, because ligands for Notch were generally believed to be unable to transmit signals into the cells expressing them. However, we showed here that Notch also supplies signals to neighboring mouse neural stem cells (NSCs). To investigate the Notch–Delta signaling pathway in a bi-directional manner, we analyzed functional roles of the intracellular domain of mouse Delta like protein 1 (Dll1IC). In developing mouse NSCs, Dll1IC, which is released from cell membrane by proteolysis, is present in the nucleus. Furthermore, we screened for transcription factors that bind to Dll1IC and demonstrated that Dll1IC binds specifically to transcription factors involved in TGF-β/Activin signaling—Smad2, Smad3 and Smad4—and enhances Smad-dependent transcription. In addition, the results of the present study indicated that over-expression of Dll1IC in embryonic carcinoma P19 cells induced neurons, and this induction was blocked by SB431542, which is a specific inhibitor of TGF-β/Activin signaling. These observations strongly suggested that Dll1IC mediates TGF-β/Activin signaling through binding to Smads and plays an important role for bi-directional Notch–Delta signaling pathway.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Delta intracellular domain mediates TGF-β/Activin signaling through binding to Smads and has an important bi-directional function in the Notch–Delta signaling pathway

Hiratochi

Nagase

Kuramochi

et al. 2007

Nucleic Acids Research

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“…While the functional significance of Delta proteolysis is not fully resolved, 12,16 the cleavage of Delta occurs either in exocytotic vesicles or at the cell surface. 17 Therefore, if trafficking of Delta to the cell surface is compromised, a decrease of cleaved Delta released to the media is expected. With Dl RF , a decrease of Dl EC in the media is observed relative to Dl WT (Fig.…”

Section: ; Ref 11)mentioning

confidence: 99%

Loss-of-Function in theDelta^RFAllele Is Due to a Failure of the Delta Protein to Reach the Cell Surface

Delwig¹,

Rand²

2007

Fly

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“…Rat monoclonal antibody 10D5 directed to the intracellular domain of Drosophila Delta was previously described (Delwig et al, 2006). Mouse monoclonal antibodies antiDelta extracellular domain (C594-9B) and anti-Notch intracellular domain (C17.9C6) and rabbit polyclonal anti-Notch extracellular domain (No.…”

Section: Antibodies and Immunohistochemistrymentioning

confidence: 99%

Delta expression in post‐mitotic neurons identifies distinct subsets of adult‐specific lineages in Drosophila

Cornbrooks

Bland

Williams

et al. 2006

Developmental Neurobiology

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ABSTRACT:The Drosophila ventral nerve cord is comprised of numerous neuronal lineages, each derived from a stereotypically positioned neuroblast (NB). At the embryonic stage the unique identities of each NB, and several of their neuronal progeny, are well characterized by spatial and temporal expression patterns of molecular markers. These patterns of expression are not preserved at the larval stage and thus the identity of adult-specific lineages remains obscure. Recent clonal analysis using MARCM has identified 24 adult-specific lineages arising from thoracic NBs at the larval stage. In this study, we have explored a role for the Delta protein in development of the post-embryonic Drosophila ventral nerve cord. We find that Delta expression identifies 7 of the 24 adult-specific lineages of the thoracic ganglia by being highly enriched in clusters of newly born postmitotic neurons and their neurite bundles. The Delta lineages constitute the majority of bundles projecting to the ventral neuropil, consistent with a role in processing leg sensory information. Targeted knockdown of Delta in neurons using RNAi results in significantly decreased leg chemosensory response and a relatively unaffected leg mechanosensory response. Delta RNAi knockdown in Delta lineages also gives a more diffuse bundle terminal morphology while the overall path-finding of neurite bundles is unaffected. We also identify a male-specific Delta lineage in the terminal abdominal ganglia, implicating a role for Delta in development of sexually dimorphic neural networks. Examples of Delta-expressing neurites contacting Notch-expressing glia are also seen, but are not common to all Delta lineages. Altogether, these data reveal a fundamental pattern of Delta expression that is indicative of an underlying developmental program that confers identity to adult lineage neurons. '

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Endocytosis-independent mechanisms of Delta ligand proteolysis

Cited by 21 publications

References 57 publications

The Delta intracellular domain mediates TGF-β/Activin signaling through binding to Smads and has an important bi-directional function in the Notch–Delta signaling pathway

The Delta intracellular domain mediates TGF-β/Activin signaling through binding to Smads and has an important bi-directional function in the Notch–Delta signaling pathway

Loss-of-Function in theDelta^RFAllele Is Due to a Failure of the Delta Protein to Reach the Cell Surface

Delta expression in post‐mitotic neurons identifies distinct subsets of adult‐specific lineages in Drosophila

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Endocytosis-independent mechanisms of Delta ligand proteolysis

Cited by 21 publications

References 57 publications

The Delta intracellular domain mediates TGF-β/Activin signaling through binding to Smads and has an important bi-directional function in the Notch–Delta signaling pathway

The Delta intracellular domain mediates TGF-β/Activin signaling through binding to Smads and has an important bi-directional function in the Notch–Delta signaling pathway

Loss-of-Function in theDeltaRFAllele Is Due to a Failure of the Delta Protein to Reach the Cell Surface

Delta expression in post‐mitotic neurons identifies distinct subsets of adult‐specific lineages in Drosophila

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Loss-of-Function in theDelta^RFAllele Is Due to a Failure of the Delta Protein to Reach the Cell Surface