Insights into mechanisms of intracellular protein turnover from studies on pinocytosis

Pinocytosis is a widespread phenomenon and involves the internalization of large amounts of plasma membrane. Much of this membrane is probably returned to the plasma membrane in vesicular form, and reasons are advanced why this recycling may occur chiefly before pinosome--lysosome fusion and may be related to vacuole fusion events. Some internalized membrane must nevertheless enter the lysosomal compartment and, in order to maintain a steady state, must be removed at the same rates as it enters. This constant lysosomal involution probably occurs by the budding of vesicles either inward (for digestion) or outward (for return to the plasma membrane). The former process allows for the transfer of cytosol components into the lysosome. Quantitative studies on pinocytosis have shown that selective substrate capture is commonly achieved by the adsorption of substances to the plasma membrane being internalized. In contrast the basal rate of uptake of liquid and membrane is not easily modified. If similar considerations apply to uptake by the quasi-pinocytic lysosomal involution, modification of proteins leading to adsorption to the cytoplasmic face of the lysosome could be the rate-determining step in the degradation of endogenous cytoplasmic proteins by lysosomes.