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Daniel Constam

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Publications associées (40)

Regulation of TGF beta and related signals by precursor processing

Daniel Constam

Secreted cytokines of the TGF beta family are found in all multicellular organisms and implicated in regulating fundamental cell behaviors such as proliferation, differentiation, migration and survival. Signal transduction involves complexes of specific ty ...

Elsevier2014

Pathogen-free husbandry conditions alleviate behavioral deficits and neurodegeneration in AD10 anti-NGF mice

Maria del Carmen Sandi Perez, Daniel Constam, Séverine Marguerite Urfer, Stamatina Tzanoulinou

It has been suggested that systemic infection, occurring during aging and chronic neurodegenerative diseases, can evoke an immune response that aggravates the progression of neurodegeneration and cognitive decline. It has been shown that the AD11 neurodege ...

2014

Nodal.Gdf1 Heterodimers with Bound Prodomains Enable Serum-independent Nodal Signaling and Endoderm Differentiation

Daniel Constam, Christophe Fuerer

The TGF beta family member Nodal is central to control pluripotent stem cell fate, but its use as a stem cell differentiation factor is limited by low specific activity. During development, Nodal depends on growth and differentiation factor (Gdf)-1 and on ...

American Society for Biochemistry and Molecular Biology2014

Furin Is the Primary in Vivo Convertase of Angiopoietin-like 3 and Endothelial Lipase in Hepatocytes

Daniel Constam

The proprotein convertases (PCs) furin, PC5/6, and PACE4 exhibit unique and/or complementary functions. Their knockout (KO) in mice resulted in strong and specific phenotypes demonstrating that, in vivo, these PCs are unique and essential during developmen ...

American Society for Biochemistry and Molecular Biology2013

Disruption of the expression of the proprotein convertase PC7 reduces BDNF production and affects learning and memory in mice

Daniel Constam

PC7 belongs to the proprotein convertase family, whose members are implicated in the cleavage of secretory precursors. The in vivo function of PC7 is unknown. Herein, we find that the precursor proBDNF is processed into mature BDNF in COS-1 cells coexpress ...

National Academy of Sciences2013

Cellular Heterogeneity During Embryonic Stem Cell Differentiation to Epiblast Stem Cells Is Revealed by the ShcD/RaLP Adaptor Protein

Daniel Constam, Anja Dietze, Antonio Simeone

The Shc family of adaptor proteins are crucial mediators of a plethora of receptors such as the tyrosine kinase receptors, cytokine receptors, and integrins that drive signaling pathways governing proliferation, differentiation, and migration. Here, we rep ...

Wiley-Blackwell2012

Automated design of ligands to polypharmacological profiles

Daniel Constam

The clinical efficacy and safety of a drug is determined by its activity profile across many proteins in the proteome. However, designing drugs with a specific multi-target profile is both complex and difficult. Therefore methods to design drugs rationally ...

Nature Publishing Group2012

Two mutations in human BICC1 resulting in Wnt pathway hyperactivity associated with cystic renal dysplasia

Daniel Constam, Anne Grapin-Botton, Marine Marie Kraus

Bicaudal C homologue 1 (Bicc1) knockout in mice causes polycystic kidney disease and pancreas development defects, including a reduction in insulin-producing β-cells and ensuing diabetes. We therefore screened 137 patients with renal abnormalities or assoc ...

2011

The microenvironment patterns the pluripotent mouse epiblast through paracrine Furin and Pace4 proteolytic activities

Daniel Constam, Christophe Fuerer

The fate of pluripotent cells in early mouse embryos is controlled by graded Nodal signals that are activated by the endoproteases Furin and Pace4. Soluble forms of Furin and Pace4 cleave proNodal in vitro and after secretion in transfected cells, but dire ...

2011

Visualization of proprotein convertase activity in living cells and tissues

Daniel Constam

The invention relates to a system for detecting the presence of a convertase cleaving activity, the system comprising a molecule comprising a proteolytic cleavage site with the amino acid sequence -R-X1-X2-R-, wherein R represents the amino acid arginine, ...

2011

Imaging proprotein convertase activities and their regulation in the implanting mouse blastocyst

Daniel Constam

Axis formation and allocation of pluripotent progenitor cells to the germ layers are governed by the TGF-β-related Nodal precursor and its secreted proprotein convertases (PCs) Furin and Pace4. However, when and where Furin and Pace4 first become active ha ...

Rockefeller University Press2010

KAP1 controls endogenous retroviruses in embryonic stem cells

Didier Trono, Daniel Constam, Pierre Maillard, Séverine Reynard, Johan Jakobsson, Sonia Verp, Helen Mary Rowe, Jacques Rougemont, Hillary Layard-Liesching

More than forty per cent of the mammalian genome is derived from retroelements, of which about one-quarter are endogenous retroviruses (ERVs). Some are still active, notably in mice the highly polymorphic early transposon (ETn)/MusD and intracisternal A-ty ...

Nature Publishing Group2010

Riding shotgun: a dual role for the epidermal growth factor-Cripto/FRL-1/Cryptic protein Cripto in Nodal trafficking

Daniel Constam

Nodal is a secreted protein of the transforming growth factor beta (TGFbeta) family that activates Smad2 and Smad3 transcription factors through complexes of type I and type II activin receptors and glycosyl-phosphatidylinositol-anchored coreceptors of the ...

2009

Intracellular trafficking and signaling in development

Daniel Constam

Tissue patterning during development relies on cell communication by secreted proteins and receptors that engage in complex signaling crosstalk to induce distinct cell behaviors in a context-dependent fashion. Here I summarize recent insights into basic me ...

2009

Running the gauntlet: an overview of the modalities of travel employed by the putative morphogen Nodal

Daniel Constam

A fundamental challenge in biology is to explain how progenitor cells in developing tissues acquire distinct fates according to their position. In vertebrates, the positional information that specifies the germ layers and the primary body axes is mediated ...

Elsevier2009

Bicaudal C, a novel regulator of Dvl signaling abutting RNA-processing bodies, controls cilia orientation and leftward flow

Daniel Constam, Charlotte Maisonneuve, Thomas Alois Weber

Polycystic diseases and left-right (LR) axis malformations are frequently linked to cilia defects. Renal cysts also arise in mice and frogs lacking Bicaudal C (BicC), a conserved RNA-binding protein containing K-homology (KH) domains and a sterile alpha mo ...

2009

VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5

Daniel Constam

We have identified an ethylnitrosourea (ENU)-induced recessive mouse mutation (Vcc) with a pleiotropic phenotype that includes cardiac, tracheoesophageal, anorectal, anteroposterior patterning defects, exomphalos, hindlimb hypoplasia, a presacral mass, ren ...

2008

Cripto localizes nodal at the limiting membrane of early endosomes

Daniel Constam, Stéphane Baflast

Cripto is a glycosylphosphatidylinositol (GPI)-anchored co-receptor of Nodal and several other transforming growth factor-beta (TGF-beta) family ligands. It contains an epidermal growth factor (EGF)-like motif and a Cripto-FRL1-Cryptic (CFC) domain, which ...

2008

Cripto promotes A-P axis specification independently of its stimulatory effect on Nodal autoinduction

Daniel Constam

The EGF-CFC gene cripto governs anterior-posterior (A-P) axis specification in the vertebrate embryo. Existing models suggest that Cripto facilitates binding of Nodal to an ActRII-activin-like kinase (ALK) 4 receptor complex. Cripto also has a crucial func ...

Rockefeller University Press2008

Cripto recruits Furin and PACE4 and controls Nodal trafficking during proteolytic maturation

Daniel Constam, Stéphane Baflast

The glycosylphosphatidylinositol (GPI)-anchored proteoglycan Cripto binds Nodal and its type I receptor Alk4 to activate Smad2,3 transcription factors, but a role during Nodal precursor processing has not been described. We show that Cripto also binds the ...

2008

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