Protein glycosylation, various mechanisms

Figure 4-4. The domain organization of an integral, transmembrane protein as well as the mechanisms for interaction of proteins with membranes. The numbers illustrate the various ways by which proteins can associate with membranes I, multiple transmembrane domains formed of a-helices 2, a pore-forming structure composed of multiple transmembrane domains 3, a transmembrane protein with a single a-helical membrane-spanning domain 4, a protein bound to the membrane by insertion into the bilayer of a covalently attached fatty acid (from the inside) or 5, a glycosyl phosphatidylinositol anchor (from the outside) 6, a protein composed only of an extracellular domain and a membrane-embedded nonpolar tail 7, a peripheral membrane protein noncova-lently bound to an integral membrane protein.

Clathrin-mediated endocytosis is a major vesicular transport mechanism in the neuron, which enables the internalization of plasma membrane-bound proteins, nutrients, hormones and other molecules associated with the plasma membrane into intracellular compartments. Clathrin and various adaptor and accessory proteins work in concert at different stages of clathrin coated vesicle formation and disassembly, and many of these proteins (such as clathrin light chain, AP-2, dynamin 1, synaptojanin 1, and the amphiphysins) are substrates for protein kinases (Korolchuk et al. 2003). In addition, it has been suggested that directing synaptotagmin 1 to the synaptic vesicle is dependent on the N-terminal glycosylation of this protein (Han et al. 2004). 

The elevated serum levels of LDL cholesterol found in patients such as Ivan Applebod who have type 2 diabetes meUitus is multifactorial. One of the mechanisms responsible for this increase involves the presence of chronically elevated levels of glucose in the blood of poorly controlled diabetics. This prolonged h5 perglycemia increases the rate of nonenzy-matic attachment of glucose to various proteins in the body, a process referred to as gly-cation or glycosylation of proteins. 

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