Secret Passions

I have always been a little intrigued by the processes that regulate how and where membranes bud or fuse or invaginate. Some of my research has touched upon this topic because unlike most secreted proteins, the endosperm storage proteins I study never exit the ER in vesicles, but are retained in highly specialized protein bodies. Therefore in my advanced cell biology course I spend a lot of time talking about the sophisticated regulation that cells have evolved to control which membrane-bound compartments go where in the cell. If you look at it as analogous to a train, bus or airplane, each passenger has a ticket that must be verified by an agent and then the carrier takes off for the final destination. A bus, in particular, usually has a visible sign on the front marking where the final destination is. The process is amazingly similar in cells. Proteins (passengers) with a specific structure (ticket) are recognized by receptors (agents), loaded on specific a “bus” called a vesicle and transported on cytoskeletal highways to the correct destination (Lysosome, golgi, endosome, plasma membrane, etc.). In the cell each “station” and “bus” are painted with specific types of phosphoinositide lipids that in association with specific receptor proteins ensure that the transportation system runs smoothly.

Why did I just pop out and describe this complex regulation? Well, other than the fact we will begin to discuss membranes, membrane transport and membrane trafficking soon:  the most recent “Editors Choice” email from Science magazine highlighted a really interesting article that, for the first time, studied the process of endocytosis in vitro! Why is this exciting? Now that these investigators have established a cell-free system they can bit by bit reduce the system to the necessary players. And why is this important? There are many diseases associated with improper transport and processing of proteins in cells and tissues and as we identify the critical players therapies can be developed. In vitro investigations of transport between the ER and Golgi were critical for understanding how the whole bus station and transportation network were regulated and organized.

A great series of lectures on the topic are given by HHMI investigator Randy Scheckman on the iBioseminars site. I think Scheckman is a serious contender for a Nobel Prize in medicine within the next few years.