Fig. 1.8 ). Pinocytosis (“cellular drinking”) is a fluid-phase process. The plasma membrane invaginates and is pinched off to form a cytoplasmic vesicle; after delivering their cargo, endocytosed vesicles recycle back to the plasma membrane (exocytosis) for another round of ingestion. Endocytosis and exocytosis are tightly balanced and highly active, as a cell typically pinocytoses 10% to 20% of its own cell volume each hour, or about 1% to 2% of its plasma membrane each minute. Pinocytosis and receptor-mediated endocytosis begin with the formation of a clathrin-coated pit containing the ligand to be internalized (by itself or bound to the receptor), which rapidly http://ebooksmedicine.net invaginates and pinches off to form a clathrin-coated vesicle. Thus, trapped within the vesicle is a gulp of the extracellular milieu, as well as receptor-bound macromolecules as described below. The vesicles then rapidly uncoat and fuse with an acidic intracellular structure called the early endosome, which progressively matures to late endosomes and ultimately fuses with lysosomes.
Receptor-mediated endocytosis is the major uptake mechanism for certain macromolecules, as exemplified by transferrin and low-density lipoprotein (LDL). These macromolecules bind to receptors that localize to clathrin-coated pits. After binding to their specific receptors, LDL and transferrin are endocytosed in vesicles that mature into early and late endosomes. In the acidic environment of the endosome, LDL and transferrin release their bound ligands (cholesterol and iron, respectively), which then exit into the cytosol, and the LDL receptor and transferrin receptor subsequently recycle to the plasma membrane. Defects in receptor-mediated transport of LDL are responsible for familial hypercholesterolemia, as described in Chapter 7.
The ability of cells to adopt a particular shape, maintain polarity, organize the intracellular organelles, and move about depends on the intracellular scaffolding of proteins called the cytoskeleton (
Fig. 1.9 ). In eukaryotic cells, there are three major classes of cytoskeletal proteins: • Actin microfilaments are fibrils 5-to 9-nm in diameter formed from the globular protein actin (G-actin), the most abundant cytosolic protein in cells. G-actin monomers noncovalently polymerize into long filaments (F-
Fig. 1.9 Cytoskeletal elements and cell–cell interactions. Interepithelial adhesion involves several different surface protein interactions, including tight junctions and desmosomes; adhesion to the ECM involves cellular integrins (and associated proteins) within hemidesmosomes. See text for details.
actin) that intertwine to form double-stranded  helices. In muscle cells, the filamentous protein myosin binds to actin and moves along it, driven by ATP hydrolysis (the basis of muscle contraction). In non-muscle cells, F-actin assembles via an assortment of actinbinding proteins into well-organized bundles and networks that control cell shape and movement.
Intermediate filaments are fibrils 10-nm in diameter that comprise a large and heterogeneous family. Members include lamins A, B, and C, which contribute to the structure of nuclear lamina. Individual types of intermediate filaments have characteristic tissue-specific patterns of expression that are useful for identifying the cellular origin of poorly differentiated tumors.
Vimentin: Mesenchymal cells (fibroblasts, endothelium) anchoring intracellular organelles
Desmin: Muscle cells, forming the scaffold on which actin and myosin contract