The dynamic interaction of AMBRA1 with the dynein motor complex regulates mammalian autophagy.

Autophagy is an evolutionary conserved catabolic process involved in several physiological and pathological processes such as cancer and neurodegeneration. Autophagy initiation signaling requires both the ULK1 kinase and the BECLIN 1-VPS34 core complex to generate autophagosomes, double-membraned vesicles that transfer cellular contents to lysosomes. In this study, we show that the BECLIN 1-VPS34 complex is tethered to the cytoskeleton through an interaction between the BECLIN 1-interacting protein AMBRA1 and dynein light chains 1/2.

A novel role for autophagy in neurodevelopment.

We recently showed that Ambra 1, a WD40-containing approximately 130 KDa protein, is a novel activating molecule in Beclin 1-regulated autophagy and plays a role in the development of the nervous system. Ambra 1 binds to Beclin 1 and favors Beclin 1/Vps34 interaction. At variance with these factors, Ambra 1 is highly conserved among vertebrates only, and its expression is mostly confined to the neuroepithelium during early neurogenesis.

Ambra1 regulates autophagy and development of the nervous system.

Autophagy is a self-degradative process involved both in basal turnover of cellular components and in response to nutrient starvation or organelle damage in a wide range of eukaryotes. During autophagy, portions of the cytoplasm are sequestered by double-membraned vesicles called autophagosomes, and are degraded after fusion with lysosomes for subsequent recycling. In vertebrates, this process acts as a pro-survival or pro-death mechanism in different physiological and pathological conditions, such as neurodegeneration and cancer; however, the roles of autophagy during embryonic development are still largely uncharacterized.

Expanding roles of programmed cell death in mammalian neurodevelopment.

Programmed cell death is an orchestrated form of cell death in which cells are actively involved in their own demise. During neural development in mammals, many progenitor cells, immature cells or differentiated cells undergo the most clearly characterized type of cell death, apoptosis. Several pathways of apoptosis have been linked to neural development, but according to the numerous and striking phenotypes observed when apoptotic genes are inactivated, the mitochondrial death-route is the most important pathway in this context.