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V Morel

Publications and source records attributed to V Morel.

5 recordsLinked to original sources

Repression by suppressor of hairless and activation by Notch are required to define a single row of single-minded expressing cells in the Drosophila embryo.

Notch signal transduction appears to involve the ligand-induced intracellular processing of Notch, and the formation of a processed Notch-Suppressor of Hairless complex that binds DNA and activates the transcription of Notch target genes. This suggests that loss of either Notch or Su(H) activities should lead to similar cell fate changes. However, previous data indicate that, in the Drosophila blastoderm embryo, mesectoderm specification requires Notch but not Su(H) activity. The determination of the mesectodermal fate is specified by Single-minded (Sim), a transcription factor expressed in a single row of cells abutting the mesoderm. The molecular mechanisms by which the dorsoventral gradient of nuclear Dorsal establishes the single-cell wide territory of sim expression are not fully understood. We have found that Notch activity is required for sim expression in cellularizing embryos. In contrast, at this stage, Su(H) has a dual function. Su(H) activity was required to up-regulate sim expression in the mesectoderm, and to prevent the ectopic expression of sim dorsally in the neuroectoderm. We have shown that repression of sim transcription by Su(H) is direct and independent of Notch activity. Conversely, activation of sim transcription by Notch requires the Su(H)-binding sites. Thus, Notch signalling appears to relieve the repression exerted by Su(H) and to up-regulate sim transcription in the mesectoderm. We propose a model in which repression by Su(H) and derepression by Notch are essential to allow for the definition of a single row of mesectodermal cells in the blastoderm embryo.

Animals↗

Towards the proteome of the rhodopsin-bearing post-Golgi compartment of retinal photoreceptor cells.

Polarized sorting of rhodopsin in retinal rod photoreceptor cells is mediated by post-Golgi carrier membranes that bud from the trans-Golgi network and fuse with the specialized domain of the plasma membrane in the rod inner segment. The identity of the majority of the resident proteins of this organelle still remains elusive, despite multifaceted approaches to study this compartment. In the present study we have taken a proteomic approach to the analysis of the post-Golgi carriers. First, we modified the previously established fractionation protocols in order to achieve greater purity of the isolated membranes. Specifically, the new fractionation scheme depleted the post-Golgi fraction of cytosolic proteins that were the most abundant contaminants complicating analysis of two-dimensional (2-D) gel profiles in our previous preparations. The isolated membranes were subjected to 2-D gel electrophoresis, immunoblotting and microsequencing. This analysis showed that the improved subcellular fractionation yielded a fraction highly enriched in rhodopsin-bearing post-Golgi carrier membranes. Two-dimensional mapping revealed 29 proteins that are preferentially found in this fraction and therefore represent candidates for post-Golgi membrane-specific proteins. This preparation of rhodopsin-bearing post-Golgi carriers is a first step towards the proteomics of this important organelle.

Amino Acid Sequence↗

Occurrence of an HIV-1 gp160 endoproteolytic activity in low-density vesicles and evidence for a distinct density distribution from endogenously expressed furin and PC7/LPC convertases.

Human immunodeficiency virus (HIV) glycoprotein (gp) 160 processing by host cell proteinases is an essential step for viral fusion and infectivity. We have identified a rat liver subcellular fraction which specifically processes gp160 into gp120 and gp41. Using equilibration of microsomes in sucrose gradients, the gp160 cleavage activity was associated with particles equilibrating at low densities, well-separated from the endoplasmic reticulum, cis-Golgi network, Golgi stacks, lysosomes and plasma membrane. Its density distribution was compatible with light secretory vesicles derived from the trans-Golgi network (TGN) or to endosomes, but association with endosomes was not supported by free flow electrophoresis. Although furin and pro-protein convertase (PC) 7/LPC have been proposed as the major gp160 processing convertases, the rat liver microsomal gp160 processing activity was essentially resolved from furin and only partially overlapped PC7/LPC. These data suggest that proteinase(s) other than furin and PC7/LPC, presumably located in TGN-derived vesicles, may participate in the gp160 processing into gp120 and gp41.

Amino Acid Sequence↗

Search for DNA sequence variations using a MutS-based technology.

The search for DNA sequence variations (DSV) is emphasized with genetic studies of a large number of multifactorial diseases. Saturation of regions of interest with diallelic polymorphisms will be an essential step to pinpoint, through association studies, predisposing genes. We have developed a solid-phase method based on the ability of mismatch binding protein MutS to recognize single nucleotide mismatches. This approach was applied to the study of 83 sequence-tagged sites (STSs) extracted from an eight centimorgans (cM) chromosome 21 region. One-third of tested STSs were found to be polymorphic leading to a frequency of one DSV every 822 base pairs (bp). Sequencing of analyzed STSs showed the high reliability of the MutS-based technology for mismatches up to 2 bp in DNA fragments ranging in size from 200 bp to 1 kilobase (kb). The entire assay which is performed in a solid-phase format without the need of electrophoresis or sequencing, will provide an efficient tool for new polymorphism detection.

Adenosine Triphosphatases↗

[Signalling by Notch family receptors].

From nematode to man, the transmembrane receptors of the Notch family act throughout embryonic and post-embryonic development to regulate the acquisition and/or maintenance of specific differentiative states. We will review here our current state of knowledge on Notch receptors structure and signalling activity.

Animals↗