Loss of the cbd-1 gene causes intracellular trafficking defects in C. elegans:

Several large scale RNAi screens in C. elegans have allowed us to develop a network of genes involved in early embryogenesis that can be broken down into molecular modules. Phenotypic analysis of the cbd-1 gene, chosen from the oocyte integrity module has helped elucidate its role in intracellular trafficking events important for fertilization and egg activation. RNAi depletion of cbd-1 prevented sperm receptor molecules EGG-1 and EGG-2 from accumulating at the oocyte plasma membrane, thereby interfering with fertilization. Similarly, yolk receptor RME-2 did not localize to the membrane and RNAi animals showed reduced yolk uptake in oocytes, causing them to be poorly developed. Yolk uptake via RME-2 is important for CAV-1 localization, which plays a role in Ras/MAPK dependent meiotic progression. RNAi of cbd-1 caused a mislocalization of CAV-1 and a meiotic arrest at metaphase I. The EGG-3/CHS-1 membrane complex also failed to form, thereby affecting regulation of MBK-2 which did not properly degrade its maternal protein targets. These RNAi experiments lead us to believe that cbd-1 functions as a general regulator, controlling trafficking of proteins to the membrane. Proper localization of cbd-1 targets to the membrane is critical to their function. The targets that we have uncovered thus far are important regulators of meiotic progression, sperm entry, eggshell formation, and egg activation events.M.S.Includes bibliographical references (p. 44-48)by Lindsay Kell