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Laure Gambardella"Deciphering PI3Kalpha signaling pathway components indispensable to brain and post-natal retina angiogenesis"

Abstract :


The total length of capillaries in an adult human brain is around 600 km.
It has now been accepted that the nervous and vascular system are functionally interdependent. The development of the vasculature depends on signals sent by the nervous system and the nervous system depends on blood flow to remain healthy. Angiogenesis is the biological process involving the growth of new blood vessels from the pre-existing vasculature. Deficient angiogenesis or vessel regression has been associated with or shown to precede neurodegenerative diseases as Alzeimer's disease, amyotrophic lateral sclerosis and diabetic neuropathy. Stimulating angiogenesis is already considered as a potential therapy of ischemic stroke and could be envisaged in the treatment of other neurological disorders. Identifying the molecular regulators of angiogenesis could provide key therapeutic targets. Unfortunately the signaling pathways modulating angiogenesis are still incompletely understood. Here we demonstrate that in the mouse, the GTPase activating protein ARAP3 is necessary to sprout new vessels from a pre-existing vascular network. ARAP3 is a dual GTPase activating protein for the small GTPases RhoA and Arf6. Our work shows that it is a direct effector of PI3kinase-alpha in the regulation of sprouting angiogenesis.

Selected publications

PI3K signaling through the dual GTPase-activating protein ARAP3 is essential for developmental angiogenesis.Gambardella L, Hemberger M, Hughes B, Zudaire E, Andrews S, Vermeren S.Sci Signal. 2010 Oct 26;3(145):ra76.

Nathalie Macrez