0000000000223856
AUTHOR
Ioanna Bethani
PHD3 regulates EGFR internalization and signalling in tumours
Tumours exploit their hypoxic microenvironment to induce a more aggressive phenotype, while curtailing the growth-inhibitory effects of hypoxia through mechanisms that are poorly understood. The prolyl hydroxylase PHD3 is regulated by hypoxia and plays an important role in tumour progression. Here we identify PHD3 as a central regulator of epidermal growth factor receptor (EGFR) activity through the control of EGFR internalization to restrain tumour growth. PHD3 controls EGFR activity by acting as a scaffolding protein that associates with the endocytic adaptor Eps15 and promotes the internalization of EGFR. In consequence, loss of PHD3 in tumour cells suppresses EGFR internalization and hy…
Ex Vivo Retinal Explant Cultures to Study Angiogenic Responses
The mouse retina has long been regarded as an easily accessible and advantageous system to investigate important questions of developmental angiogenesis. The protocol presented here profits from the suitability of the mouse retina as experimental model and describes an ex vivo culture technique of mouse retina explants that allows the quantitative assessment of angiogenic responses to pharmacological manipulations. The technique involves the extraction of the retina from the intact eye, the immediate flat mounting of the tissue on a hydrophilic membrane and the acute stimulation or inhibition of angiogenic processes of the developing vessels in their physiological context ex vivo. The numbe…
Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system.
Developing the bloodbrain barrier During development, signals need to be dynamically integrated by endothelial cells, neurons, and glia to achieve functional neuro-glia-vascular units in the central nervous system. During cortical development, neuronal Dab1 and ApoER2 receptors respond to a guidance cue called reelin. Studying mice, Segarra et al. found that Dab1 and ApoER2 are also expressed in endothelial cells (see the Perspective by Thomas). The integration of reelin signaling in endothelial cells and neurons facilitates the communication between vessels, glia, and neurons that is necessary for the correct positioning of neurons during cortical development. This integration is also impo…