Normally when we see a receptor on the surface of a cell (such as the receptor for Vascular Endothelial Growth Factor — VEGF) we assume that when its ligand binds, something happens inside the cell. Not always so, says Cell vol. 159 pp. 473 – 474, 584 – 596 ’14. VEGF is crucial in fetal development (inactivation of just one of the two copies of the gene is lethal for the mouse embryo [ PNAS vol. 95 pp. 14389 – 14394 98 ]).
One of the problems in diabetic retinopathy is proliferation of retinal blood vessels. For those who don’t already know — light outside the eye has to pass through all 10 cellular layers of the retina before it hits the photoreceptors which can absorb it. So more vessels in the neuronal layers isn’t good.
The Cell paper shows that in the developing retina, VEGF is depleted near neurons, by neuronal engulfment of the VEGF/VEGF receptor complex and degradation. The complex doesn’t do anything metabolically to the neuron. This prevents misdirected angiogenesis into the neuronal plane.
This turns what we’ve always thought about receptors on the cell surface on its head — they must be doing something inside the cell, when a ligand binds to them. Apparently not always.