Protein Recycling (Signal Pathways)

Some intercellular proteins are needed to respond to specific extracellular signals. These proteins must be stored, recycled and kept available during the periods of time in between the arrival of such extracellular signals.

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Glucose is an important sugar source in humans. As the precursor for glycolysis, it is at the beginning of the chemical chain that leads to the production of ATP, the universal energy molecule.

In humans, most of the glucose is utilized in muscle and fat tissues. When we exercise, glucose is rapidly taken up to support our muscles. After eating, the circulated glucose is taken up by fat cells and used immediately or stored as glycogen for later use.

The cells in these two tissue types have a common mechanism for taking up glucose. When glucose levels rise in these tissues, the glucose transporter 4 (or GLUT4) protein is mobilized from the cytoplasm and deposited in the plasma membrane.

This animation illustrates how proteins are recycled in the cell, a basic concept critical to understanding how external signals affect protein trafficking.

As illustrated in the Protein Trafficking animation, many proteins are processed through the Golgi apparatus and the trans-Golgi network, and eventually stored in vesicles. The vesicles are membrane-bound cargo vessels that can move to different cellular locations.

Here we focus on glucose transporter 4 (again GLUT4), the main protein through which glucose moves into the cell in humans. The glucose transporter proteins are found in two locations. One portion is found in the plasma membrane. The second pool of GLUT4 proteins are found in GLUT4 storage vesicles (or GSVs). This is a pool of vesicles that cluster together.

When glucose levels are low in muscle and fat tissues, only a small portion of the cellular GLUT4 protein is found in the plasma membrane. The vast majority (about 90%) is found in GLUT4 storage vesicles (or GSVs). The membrane bound GLUT4 proteins are needed to transport even the low level of glucose into the cell. Here you can see a few glucose molecules moving into the cell.

There is a steady recycling of the plasma membrane GLUT4 protein pool. These proteins bud off and move to the GSV pool in a membrane vesicle. The membrane pool is refilled by the movement of vesicles from the GSV pool to the plasma membrane where the vesicle merges and the GLUT4 protein is embedded in the membrane.

Recycling is a common feature of protein stored in vesicles that balances the current need for a certain protein and the ability to rapidly mobilize that protein to its site of action when the proper signal is received. An additional animation will show what happens in muscle and fat cells when they are stimulated by insulin.

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Major funding provided by the National Science Foundation.

Additional funding provided by the U.S. Department of Education's Fund for the Improvement of Postsecondary Education.

With support from Autodesk's® Academy Award® winning 3-D animation and effects software Maya®.