Built to Recycle

One of the neat things about cells is the way they are built to recycle. For example, protein function is largely due to the shape of the protein. Yet cell’s do not need a large, stored set of 3D-casting templates to form the shaped macromolecules. The 3D information comes from the sequence of amino acids. Thus, to build a protein, all the cell has to do is a) string together amino acids b) in the right order. And both functions are carried out by the ribosome (where each function is carried out by one of the ribosomal subunits).

Yet there is another dimension to this process. Such 3D structures can be easily disassembled into their amino acid subunits and these same amino acids can be used to build another protein. The whole system is built to perfectly facilitate recycling, which makes in increasingly difficult to characterize the flux of protein synthesis and degradation as “wasteful.” On the contrary, this very flux is part of the amazing versatility and flexibility of the cell.

Anyway, recent research has moved this theme of recycling to membrane proteins.

Scott Emr, who is director of the Weill Institute for Cell and Molecular Biology at Cornell, along with his colleagues, have played a lead role in this area.

“We are interested in understanding how cells deal with garbage,” said Emr. “It’s really a very sophisticated recycling system.”

Emr’s paper in Cell identifies a family of proteins that controls the removal of unwanted water-insoluble proteins from the membrane. The research advances understanding of how cells recognize which proteins out of hundreds on a cell’s surface should be removed.

Typically, when the problem is one of specification or location, a set of protein involved in machine-like behavior will be involved. This case is no different:

The researchers, including postdoctoral fellows Jason MacGurn and Chris Stefan, identified nine related proteins in yeast, which they named the “arrestin-related trafficking” adaptors or ARTs. Each of these proteins identifies and binds to a different set of membrane proteins. Once bound, the ART protein links to an enzyme that attaches a chemical tag for that protein’s removal. The ARTs are found in both yeast and humans, suggesting the fundamental nature of their function.

Once the protein is tagged, the piece of membrane with the targeted protein forms a packet, called a vesicle, that enters the cell’s cytoplasm. There, the vesicle enters a larger membrane body called an endosome, which in turn dumps it into another compartment called the lysosome, where special enzymes break apart big molecules to their core units: proteins to amino acids, membranes to fatty acids, carbohydrates to sugars and nucleic acids to nucleotides, and those basic materials are then reused.
The paper in Developmental Cell, co-authored by Emr with postdoctoral fellows David Teis and Suraj Saksena, describes for the first time how a set of four proteins assemble into a highly ordered complex. This complex encircles membrane proteins that must be disposed of in the lysosome. Emr’s lab was the first to identify and characterize these protein complexes (known as ESCRTs). The Developmental Cell paper describes the order of events in which the ESCRT complexes encircle and deliver “waste” proteins into vesicles destined for recycling in the lysosome.

A very sophisticated, and ancient, recycling system indeed.


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