FIGURE 2.7 • Movement of molecules through the plasma membrane. Fat-soluble and other small, uncharged molecules (in green) cross the plasma membrane by simple diffusion down their concentration gradient. Other molecules require membrane transport proteins to provide them with individual passage across the plasma membrane. Small water-soluble molecules (in blue) require highly selective carrier proteins to transfer them across the plasma membrane. After binding with a molecule, the carrier protein undergoes a series of conformational changes and releases the molecule on the other side of the membrane. If the process requires energy, it is called active transport (e.g., transport of H ions against their concentration gradient). The process is called passive transport when energy is not required (e.g., glucose transport). Ions and other small charged molecules (in red) are transported through the plasma membrane by ion-selective channel proteins. In neurons, for instance, ion transport is regulated by membrane potentials (voltage-gated ion channels); in skeletal muscle cells, neuromuscular junctions possess ligand-gated ion channels.
muscle cells), or mechanical stress (e.g., mechanically gated ion channels in the internal ear).
Vesicular transport maintains the integrity of the plasma membrane and also provides for the transfer of molecules between different cellular compartments.
Some substances enter and leave cells by vesicular transport, a process that involves configurational changes in the plasma membrane at localized sites and subsequent formation of vesicles from the membrane or fusion of vesicles with the membrane (Fig. 2.8).
The major mechanism by which large molecules enter, leave, and move within the cell is called vesicle budding. Vesicles formed by budding from the plasma membrane of one compartment fuse with the plasma membrane of another compartment. Within the cell, this process ensures intercompartmental transfer of the vesicle contents.
Vesicular transport involving the cell membrane may also be described in more specific terms:  Endocytosis is the general term for processes of vesicular transport in which substances enter the cell.  Exocytosis is the general term for processes of vesicular transport in which substances leave the cell.
Both processes can be visualized with the electron microscope.
FIGURE 2.8 • Endocytosis and exocytosis are two major forms of vesicular transport. Endocytosis brings molecules and other substances into the cell. In exocytosis, synthesized molecules and other substances leave the cell. Endocytosis is associated with the formation and budding of vesicles from the plasma membrane; exocytosis is associated with the fusion of vesicles originating from intracellular organelles with the plasma membrane, and it is a primary secretory modality.
Uptake of ﬂuid and macromolecules during endocytosis depends on three different mechanisms.
Some of the endocytotic mechanisms require special proteins during vesicle formation. The best known protein that interacts with the plasma membrane in vesicle formation is clathrin. Therefore, endocytosis can also be classified as either clathrin dependent or clathrin independent. In  general, three mechanisms of endocytosis are recognized in the cell:  Pinocytosis [Gr., cell drinking] is the nonspecific ingestion of ﬂuid and small protein molecules via small vesicles, usually smaller than 150 nm in diameter. Pinocytosis is performed by virtually every cell in the organism, and it is constitutive (i.e., it involves a continuous dynamic formation of small vesicles at the cell surface (Fig. 2.9a). Recent studies indicate that mechanoenzymes such as GTPase (dynamin) are involved in pinocytotic vesicle scission (the process of pinching off from the plasma membrane). Pinocytotic vesicles are visible with the TEM, and they have a smooth surface. These smooth pinocytotic vesicles are especially numerous in the endothelium of blood vessels (Fig. 2.9b) and in smooth muscle cells. Pinocytosis does not require clathrin and