Endocytic recycling

Abstract

A typical fibroblast cell is estimated to internalize at least 2% of its plasma membrane into endosomes per minute. The return of membrane from endosomes to the cell surface is necessary for the maintenance of membrane homeostasis. Some membrane proteins (for example, activated growth-factor receptors, the low-density-lipoprotein receptor and the transferrin receptor) are internalized by a concentrative mechanism in which the receptors are localized to specialized, clathrin-coated regions of the plasma membrane. Concentration in clathrin-coated pits is determined by the interaction of specific sequences (motifs) in the cytoplasmic domains of the proteins with elements of the coated pits. There are two main fates for materials that are internalized into sorting endosomes — they can be delivered to degradative late endosomes and lysosomes or returned to the plasma membrane. Most membrane proteins are returned to the cell surface by a mechanism that, unlike internalization through clathrin-coated pits, is not generally dependent on a specific sequence that signals a protein for recycling. In fact, the efficient targeting of a membrane protein to late endosomes or other intracellular destinations requires a specialized targeting motif. Most non-membrane-bound material inside sorting endosomes (for example, low-density lipoprotein) is delivered to late endosomes and lysosomes. As well as to internalize nutrient receptors and activated receptors, endocytic uptake has an important role in the retrieval of transmembrane proteins of the biosynthetic organelles. The localization of many proteins to these organelles is based on a dynamic retrieval process. In addition to constitutive endocytic uptake and recycling, the trafficking some proteins through the endosomal system is regulated. Regulated trafficking provides a means by which a cell can rapidly and specifically modulate the expression of proteins on the plasma membrane. One important example of this is the regulation by insulin of the GLUT4 glucose transporter on the surface of fat and muscle cells.