Peter Orlean and Anant K. Menon describe how a lipid that helps proteins attach to cell membranes is made. The protein, called glycosylphosphatidylinositol (GPI), is important because people with defective GPI can develop seizures, have heart attacks, and acquire a hemolytic condition in which red blood cells are destroyed.
Also, elevated levels of certain proteins involved in GPI anchoring have been linked to breast and bladder cancers.
GPI synthesis is initiated on the cytoplasmic side of the membrane of the endoplasmic reticulum (ER), then the resulting precursor molecule flips inside the ER, where further molecules are progressively added to it to form the complete GPI. The GPI is then linked to a protein, and the lipid-modified protein then leaves the ER for the cell membrane, where it is anchored on the outer side of the membrane via its GPI.
Orlean and Menon review the latest findings on GPI assembly in the ER, its transfer to a protein, and the changes made to GPI on its way to the cell membrane. They describe the enzymes and chemical reactions involved and highlight questions that need to be addressed, especially how GPI structure affects the proteins they carry with them and how the various components of the GPI anchoring machinery work together. Answering these questions would not only help better understand GPI assembly, but could also lead to new drugs against diseases associated with defective GPI.-American Society for Biochemistry and Molecular Biology
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