POLARITY · Role of Crumbs 3 and its partners in vesicular transport and ciliogenesis
FP6 — Marie Curie Actions (Human Resources and Mobility)
- Duration
- 2007-02-01 → 2009-01-31
- EU contribution
- €80,000
- Participants
- 1
- Scheme
- EIF
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Results in brief
Final Activity Report Summary - POLARITY (Role of Crumbs 3 and its partners in vesicular transport and ciliogenesis)
The aim of this project was to unravel the cellular and molecular role of the polarity proteins of the Crumbs family and some of their partners in retina morphogenesis and physiology in normal and pathological conditions. More precisely, we wanted to analyse the mechanism of action of the proteins of the human Crb3a complex and partners in the vesicular transport underlying the morphogenesis of the apical membrane and primary cilium in human retinal cells. Our results demonstrate a role of the human Crb3a and one of its new partners in secretion of soluble proteins and in the biogenesis of the primary cilium in a human retinal cell line ARPE19. We have extensively characterized one of the mechanisms of action during the biogenesis of the primary cilium and set up new tools to study the role of proteins in vesicular transport underlying primary cilium biogenesis in cultured cells.
Data: CORDIS, © European Union
Project objective
One person in 3000 in the world suffers from Retinis Pigmentosa, which leads to degeneration of essential cells of retina: the polarized photosensitive cells or photoreceptors. Several forms of Retinis Pigmentosa can cause partial or total blindness.Their origin is still unknown and there is no efficient therapy to cure or even prevent them. Numerous studies have shown that CRB1, one of the 3 genes encoding for the human family of proteins CRUMBS (Crb1, 2 and 3), is mutated in 60% of patients suffering from a severe form of autosomal recessive Retinis Pigmentosa called RP12. Other reports implicate Crb3 in vesicular transport at the apical membrane of epithelial polarized cells and at the tight junctions between those cells. The function and regulation of the Crumbs family of proteins are unknown.However, it has been shown that Crb2 and Crb3 are necessary for the formation of the primary cilium at the apical membrane of epithelial cells. The physiological role of the primary cilium remains elusive. Interestingly, several proteins that are localized to the primary cilium are responsible, when mutated, for diseases like the Bardet-Biedl syndrome, polycystic kidney disease or Retinis Pigmentosa. The aim of this project is to study the cellular and molecular role of the Crumbs protein family in morphogenesis and physiology of the retina.We want to understand the mechanisms by which the Crumbs proteins are necessary for cell polarity establishment by the formation and the maintenance of the apical membrane, the tight junctions, as well as the primary cilium. More precisely, we will seek for the role of Crb3 and its partners in the apical membrane morphogenesis and physiology, in epithelial cells in general, and in photoreceptors in particular.The results of this research should allow the opening of new avenues for molecular and genetic studies on human retina degeneration and lead to new strategies for therapy against Retinis Pigmentosa and other degeneration diseases.
Original text from CORDIS.
Participants
- CENTRE NATIONAL POUR LA RECHERCHE SCIENTIFIQUE · MONTPELLIERCoordinatorCity levelFrance
Links
Data: CORDIS, © European Union