Seminar Title: Retinal Phosphoinositides
Time: 3 p.m. via Zoom
Speaker Bio: Dr. Theodore Wensel is the Robert A. Welch Chair in Chemistry, chair of biochemistry at Baylor College of Medicine. His research focuses on vision research, including visual transduction, G protein-coupled receptors, phosphoinositide signaling, RGS proteins, biomembranes, ocular proteomics and gene repair.
Seminar Summary: Phosphoinositides, the phosphorylated forms of the membrane lipid phosphatidylinositol, play important roles in signal transduction and membrane trafficking. We have found that in rod cells, light exposure leads to dramatic increases in levels of phosphatidylinositol-3-phosphate (PI(3)P) and phosphatidylinositol-4,5-bisphosphate (PI(4,5)P2). We have knocked out the gene (Vps34 aka Pik3c3) encoding the Type III PI-kinase responsible for synthesis of PI(3)P in rods, cones, ON-bipolar cells and RPE cells. In all three cell types, development proceeds normally, but there are defects in autophagy, endosome processing and phagocytosis that lead to cell death. Surprisingly PI(3)P is not required for initiation of autophagy or phagocytosis, but is essential for fusion with lysosomes. PI(4,5)P2 is found in discrete patches in the plasma membrane of rod outer segments, rod inner segments, the outer nuclear layer, and peri-synaptic membranes. Its levels in the light are reduced in the absence of phototransduction, but the mechanism and functions of the light-induced changes remain under investigation. The type I PI-3 kinase responsible for synthesis of PI(3,4,5)P2 does not appear to be important for rod function or survival.