Do the signalling proteins for angiogenesis exist as a modular complex? The case for the angosome.
The vasculature remains quiescent during much of adult life, but new blood vessels can be rapidly produced when required by a process referred to as angiogenesis. Angiogenesis involves a complex series of events including the proliferation, migration, differentiation and apoptosis of capillary endothelial cells, as well as changes in vascular permeability. This hypothesis argues that in the quiescent vasculature the many factors that regulate angiogenesis are normally held together as part of an inactive modular unit, and that when angiogenesis is stimulated the modular unit dissociates thus enabling angiogenic regulators to become active. I have termed this modular unit the "angosome". It is proposed that the angosome is present in the caveolae of capillary endothelial cells. Caveolae are flask-shaped invaginations in the plasmalemma that compartmentalise signalling molecules. Endothelial cells are particularly rich in caveolae. Many of the structural and functional aspects of caveolae are controlled by the protein caveolin, one form of which, caveolin-1, interacts directly or indirectly with most of the regulatory molecules involved in angiogenesis. Caveolin-1 forms oligomers of 14-16 sub-units and I propose that oligomers of caveolin-1 form the scaffold that holds together the angosome. There is evidence that caveolin-1 is up-regulated in the differentiated, quiescent vasculature and down-regulated in proliferating endothelial cells. Since the presence of caveolin-1 can inhibit pro-angiogenic factors, it may act as a "master-switch" co-ordinating events during angiogenesis. Thus when the vasculature is quiescent the angosome may hold angiogenic factors in an inactive state and when angiogenesis is required, the angosome must disassociate to enable angiogenic factors to become active.
Department of Biosciences, University of Hertfordshire, Hatfield, Herts., AL10 9AB, UK. r.hoffman@herts.ac.uk
R
R
Hoffman
D042501:Angiogenic Proteins / Q000378:metabolism*; D000818:Animals; D021941:Caveolae / Q000502:physiology*; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D018919:Neovascularization, Physiologic / Q000502:physiology*; D021382:Protein Sorting Signals / Q000502:physiology*; D021381:Protein Transport / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
D042501:Angiogenic Proteins; C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D021382:Protein Sorting Signals