The Role of Caveolae Rafts in gSecretase Activity

The g-secretase complex was also shown to be associated with rafts [131,132], mainly in the late-Golgi and post-Golgi-derived vesicles as well as in recycling endosomes, but not in plasma membrane rafts [95,132,133].

A recent report showed that despite g-secretase cleavage occurring in lipid rafts, g-secretase catalytic activity is independent of the presence of cholesterol [133,134]. Indeed, although biochemical assays in neuronal cells showed mature g-secretase to be associated with lipid rafts in a cholesterol-dependent manner when cholesterol was acutely depleted using mbCD, the quantities of Ab produced were not altered.

In addition, it has been proposed that g-cleavage of APP could also occur following endocytosis, resulting in the intracellular generation of Ab that could be either retained in intracellular compartments or released from recycling endosomes [115]. This balance of intracellular versus cell-surface Ab generation could be regulated by the half-life of APP at the cell surface.

The current data therefore support two different possibilities for APP g-cleav-age:

• g-cleavage occurs within cholesterol-rich lipid rafts in an intracellular compartment such as early/recycling endosomes, late-Golgi and post-Golgi-derived vesicles; or

• g-cleavage of APP occurs at the cell surface outside rafts (see Fig. 10.4).

222 | 10 Lipid Rafts in Trafficking and Processing of Prion Protein and Amyloid Precursor Protein 10.4.6

Essentials of Human Physiology

Essentials of Human Physiology

This ebook provides an introductory explanation of the workings of the human body, with an effort to draw connections between the body systems and explain their interdependencies. A framework for the book is homeostasis and how the body maintains balance within each system. This is intended as a first introduction to physiology for a college-level course.

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