Different Requirements for Proteolytic Processing of Bone Morphogenetic Protein 5/6/7/8 Ligands in Drosophila melanogaster

Fritsch, Cornelia; Sawala, Annick; Harris, Robin E.; Maartens, Aidan; Sutcliffe, Catherine; Ashe, Hilary L.; Ray, Robert P.

doi:10.1074/jbc.m111.316745

Cited by 22 publications

(29 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We recently determined the N-termini of the other two Drosophila BMP ligands, Scw and Glass bottom boat (Gbb) (14). Sequence alignment reveals that the Scw and Gbb ligand domains lack the basic stretch found in the S1 form of Dpp ( Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Cu-inducible Scw and Gbb constructs (pMT-Scw-1xFLAG and pMT-Gbb-3xFLAG) (14), DppΔN-HA (21), and pGEX4T1-VkgC (11) have been described. The coding sequences of Dpp-HA (10) and Sog-Myc (19) were inserted into pMT-V5/His-A (Life Technologies) and then modified by PCR to introduce deletions or mutations (details available on request).…”

Section: Methodsmentioning

confidence: 99%

“…Scw-FLAG, Gbb-FLAG, Dpp-HA, and SogMyc proteins were produced in Drosophila S2R + cells by effectene-mediated transient transfection followed by Cu-induction as described (14). Sog-CR4 was expressed in S2 cells, because secretion from S2R + cells was inefficient.…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Multistep molecular mechanism for Bone morphogenetic protein extracellular transport in the Drosophila embryo

Sawala

Sutcliffe

Ashe

2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

In the Drosophila embryo, formation of a bone morphogenetic protein (BMP) morphogen gradient requires transport of a heterodimer of the BMPs Decapentaplegic (Dpp) and Screw (Scw) in a protein shuttling complex. Although the core components of the shuttling complex-Short Gastrulation (Sog) and Twisted Gastrulation (Tsg)-have been identified, key aspects of this shuttling system remain mechanistically unresolved. Recently, we discovered that the extracellular matrix protein collagen IV is important for BMP gradient formation. Here, we formulate a molecular mechanism of BMP shuttling that is catalyzed by collagen IV. We show that Dpp is the only BMP ligand in Drosophila that binds collagen IV. A collagen IV binding-deficient Dpp mutant signals at longer range in vivo, indicating that collagen IV functions to immobilize free Dpp in the embryo. We also provide in vivo evidence that collagen IV functions as a scaffold to promote shuttling complex assembly in a multistep process. After binding of Dpp/ Scw and Sog to collagen IV, protein interactions are remodeled, generating an intermediate complex in which Dpp/Scw-Sog is poised for release by Tsg through specific disruption of a collagen IV-Sog interaction. Because all components are evolutionarily conserved, we propose that regulation of BMP shuttling and immobilization through extracellular matrix interactions is widely used, both during development and in tissue homeostasis, to achieve a precise extracellular BMP distribution.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Multistep molecular mechanism for Bone morphogenetic protein extracellular transport in the Drosophila embryo

Sawala

Sutcliffe

Ashe

2012

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition to detecting ligands for which no antibody is available, tagged constructs can permit live analysis and allow detection of mutant variants. For mature BMP ligands, bioactive tagged versions are available for Dpp (HA and GFP) [37–39], Gbb (Flag, GFP and Venus) [40–42] and Scw (Flag) [40]. The processing and secretion of TGF-β ligands may impose restrictions on the location of useful tags for some ligands.…”

Section: Ligandsmentioning

confidence: 99%

Strategies for exploring TGF-β signaling in Drosophila

Peterson

O’Connor

2014

Methods

View full text Add to dashboard Cite

The TGF-beta pathway is an evolutionarily conserved signal transduction module that mediates diverse biological processes in animals. In Drosophila, both the BMP and Activin branches are required for viability. Studies rooted in classical and molecular genetic approaches continue to uncover new developmental roles for TGF-beta signaling. We present an overview of the secreted ligands, transmembrane receptors and cellular Smad transducer proteins that comprise the core pathway in Drosophila. An assortment of tools have been developed to conduct tissue-specific loss and gain-of-function experiments for these pathway components. We discuss the deployment of these reagents, with an emphasis on appropriate usage and limitations of the available tools. Throughout, we note reagents that are in need of further improvement of development, and signaling features requiring further study. A general theme is that comparison of phenotypes for ligands, receptors, and Smads can be used to map tissue interactions, and to separate canonical and non-canonical signaling activities. Core TGF-beta signaling components are subject to multiple layers of regulation, and are coupled to context-specific inputs and outputs. In addition to fleshing out how TGF-beta signaling serves the fruit fly, we anticipate that future studies will uncover new regulatory nodes and modes and will continue to advance paradigms for how TGF-beta signaling regulates general developmental processes.

show abstract

“…A ‘Chordin-like’ Sog cannot ensure robust Drosophila patterning [49]. Also, Gbb or Tlr, the ancestral BMP pathway components, cannot replace Scw or Tld during early patterning [23,58]*. Thus, acquisition of BMP-dependence for Sog destruction by Tlds may represent a process of canalized development.…”

Section: Sog/chordin – and Evolution Of Shuttling Mechanismsmentioning

confidence: 99%

Fine-tuned shuttles for bone morphogenetic proteins

Wharton

Serpe

2013

Current Opinion in Genetics & Development

View full text Add to dashboard Cite

Bone morphogenetic proteins (BMPs) are potent secreted signaling factors that trigger phosphorylation of Smad transcriptional regulators through receptor complex binding at the cell-surface. Resulting changes in target gene expression impact critical cellular responses during development and tissue homeostasis. BMP activity is tightly regulated in time and space by secreted modulators that control BMPs extracellular distribution and availability for receptor binding. Such extracellular regulation is key for BMPs to function as morphogens and/or in the formation of morphogen activity gradients. Here, we review shuttling systems utilized to control the distribution of BMP ligands in tissue of various geometries, developing under different temporal constraints. We discuss the biological advantages for employing specific strategies for BMP shuttling and roles of varied ligand forms.

show abstract

Different Requirements for Proteolytic Processing of Bone Morphogenetic Protein 5/6/7/8 Ligands in Drosophila melanogaster

Cited by 22 publications

References 46 publications

Multistep molecular mechanism for Bone morphogenetic protein extracellular transport in the Drosophila embryo

Multistep molecular mechanism for Bone morphogenetic protein extracellular transport in the Drosophila embryo

Strategies for exploring TGF-β signaling in Drosophila

Fine-tuned shuttles for bone morphogenetic proteins

Contact Info

Product

Resources

About