Collaboration sheds light on assembly of transporter associated with cholesterol, breast cancer, and HIV

Boston, MA--June 12, 1999--A collaboration between researchers in Great Britain, Italy, and Harvard has developed a newly detailed view of one of the cell's major transport vehicles responsible for shuttling into the cell a range of important molecules, including cholesterol.

The findings, presented in the June Molecular Cell, provide insight into how this machine, the clathrin-coated vesicle, is formed, stays together, and falls apart.

A video of the clathrin protein can be viewed on the Web at www.hms.harvard.edu/news/clathrin/. Clathrin-coated vesicles are constantly assembling and disassembling to perform their task of transporting proteins from the outside of the cell inside. They are responsible for importing LDL cholesterol, and they play a role in breast cancer through internalization of a key receptor.

During disease progression of HIV infection, clathrin-coated vesicles are subverted by a viral protein to cause down-regulation of the viral receptor CD4 in an important but not fully understood step. These molecules, and a wide range of others, are selectively trapped in the clathrin-coated vesicle for import into the cell.

The new insights into how the vesicle forms help build a picture of the overall process and suggest possible targets for future therapeutic intervention.

One mystery of clathrin vesicles is how the outer cage of clathrin assembles so rapidly. Vesicles are incessantly assembled and disassembled at an incredible scale. In the brain, where neurotransmitters are constantly released into synapses, the membrane used to export the neurotransmitters is constantly being dragged back in by clathrin-coated vesicles.

"The equivalent of the entire brain, or a football field of membrane, is turned over every hour," says
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Contact: Peta Gillyatt
gillyatt@hms.harvard.edu
617-432-0443
Harvard Medical School
18-Jun-1999