Role of Scyl1 in the early secretory pathway

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The information encoded in the human genome is translated into proteins, which are the building blocks for cells and carry out all cellular activities. Certain classes of proteins reside in cell membranes or are secreted from cells. These proteins are processed in a series of intracellular membranes that are collectively known as the secretory pathway. The earliest station of this pathway is the endoplasmic reticulum, where proteins are subjected to an initial quality control. From there, they are packaged into vesicles that carry them to the next station, the Golgi apparatus where they are modified by the addition of sugars. As vesicles are generated at the endoplasmic reticulum they often incorporate proteins that should reside in the endoplasmic reticulum. Thus, these proteins need to be returned from the Golgi back to the endoplasmic reticulum. A separate class of vesicles called COPI vesicles mediates this "retrograde" pathway. COPI-mediated retrograde trafficking is a fundamental process found in all animal cells and yet surprisingly, the molecular underpinnings of this process remain poorly defined. The studies in this proposal will reveal substantial new information regarding the molecular basis for the formation and function of COPI vesicles.