Biomedical subjects

Ellen K LeMosy

Publications and source records attributed to Ellen K LeMosy.

5 recordsLinked to original sources

PubMed2006

Spatially dependent activation of the patterning protease, Easter.

The dorsoventral axis of the Drosophila embryo is established by the activating cleavage of a signaling ligand by a serine protease, Easter, only on the ventral side of the embryo. Easter is the final protease in a serine protease cascade in which initial reaction steps appear not to be ventrally restricted, but where Easter activity is promoted ventrally through the action of a spatial cue at an unknown step in the pathway. Here, biochemical studies demonstrate that this spatial control occurs at or above the level of Easter zymogen activation, rather than through direct promotion of Easter's catalytic activity against the signaling ligand.

Animals↗

PubMed2006

Minor proteins and enzymes of the Drosophila eggshell matrix.

The Drosophila eggshell provides an in vivo model system for extracellular matrix assembly, in which programmed gene expression, cell migrations, extracellular protein trafficking, proteolytic processing, and cross-linking are all required to generate a multi-layered and regionally complex architecture. While abundant structural components of the eggshell are known and are being characterized, less is known about non-abundant structural, regulatory, and enzymatic components that are likely to play critical roles in eggshell assembly. We have used sensitive mass spectrometry-based analyses of fractionated eggshell matrices to validate six previously predicted eggshell proteins and to identify eleven novel components, and have characterized the expression patterns of many of their mRNAs. Among these are several putative structural or regulatory (non-enzymatic) proteins, most larger in mass than the major eggshell proteins and often showing preferential expression in follicle cells overlying specific structural features of the eggshell. Of particular note are the putative enzymes, some likely to be involved in matrix cross-linking (two yellow family members previously implicated in eggshell integrity, a heme peroxidase, and a small-molecule oxidoreductase) and others possibly involved in matrix proteolysis or adhesion (proteins related to cathepsins B and D). This work provides a framework for future molecular studies of eggshell assembly.

Animals↗

PubMed2006

Proteolytic regulatory mechanisms in the formation of extracellular morphogen gradients.

Growth factors are secreted into the extracellular space, where they encounter soluble inhibitors, extracellular matrix glycoproteins and proteoglycans, and proteolytic enzymes that can each modulate the spatial distribution, activity state, and receptor interactions of these signaling molecules. During development, morphogenetic gradients of these growth factors pattern fields of cells responsive to different levels of signaling, creating such structures as the branched pattern of airways and vasculature, and the arrangement of digits in the hand. This review focuses specifically on the roles of proteolytic enzymes and their regulators in the generation of such activity gradients. Evidence from Drosophila developmental pathways provides a detailed understanding of general mechanisms underlying proteolytic control of morphogen gradients, while recent studies of several mammalian growth factors illustrate the relevance of this proteolytic control to human development and disease.

Animals↗

PubMed2003

Pattern formation: the eggshell holds the cue.

Recent data indicate that Torsolike, a spatial cue for patterning terminal structures of a Drosophila embryo, is stably anchored in the fruitfly eggshell; an as yet unidentified factor is required for the high activity of Torsolike at the embryo termini.

Animals↗

PubMed2002

Three-dimensional models of proteases involved in patterning of the Drosophila Embryo. Crucial role of predicted cation binding sites.

Three-dimensional models of the catalytic domains of Nudel (Ndl), Gastrulation Defective (Gd), Snake (Snk), and Easter (Ea), and their complexes with substrate suggest a possible organization of the enzyme cascade controlling the dorsoventral fate of the fruit fly embryo. The models predict that Gd activates Snk, which in turn activates Ea. Gd can be activated either autoproteolytically or by Ndl. The three-dimensional models of each enzyme-substrate complex in the cascade rationalize existing mutagenesis data and the associated phenotypes. The models also predict unanticipated features like a Ca(2+) binding site in Ea and a Na(+) binding site in Ndl and Gd. These binding sites are likely to play a crucial role in vivo as suggested by mutant enzymes introduced into embryos as mRNAs. The mutations in Gd that eliminate Na(+) binding cause an apparent increase in activity, whereas mutations in Ea that abrogate Ca(2+) binding result in complete loss of activity. A mutation in Ea predicted to introduce Na(+) binding results in apparently increased activity with ventralization of the embryo, an effect not observed with wild-type Ea mRNA.

Animals↗