FIGURE 2.11 • Receptor-mediated endocytosis. a. This diagram shows the steps in receptor-mediated endocytosis, a transport mechanism that allows selected molecules to enter the cell. Cargo receptors recognize and bind specifc molecules that come in contact with the plasma membrane. Cargo receptor–molecule complexes are recognized by adaptin, a protein that helps select and gather appropriate complexes in specifc areas of the plasma membrane for transport into cells. Clathrin molecules then bind to the adaptin–cargo receptor–molecule complex to assemble into a shallow basketlike cage and form a coated pit. Clathrin interactions then assist the plasma membrane to change shape to form a deep depression, a fully formed coated pit that becomes pinched off from the plasma membrane by the protein complex dynamin as a coated vesicle (i.e., budding from the membrane). Selected cargo proteins and their receptors are thus pulled from the extracellular space into the lumen of a forming coated vesicle. After budding and internalization of the vesicle, the coat proteins are removed and recycled for further use. The uncoated vesicle travels to its destination to fuse with a cytoplasmic organelle. b. Electron micrograph of the cytoplasmic surface of the plasma membrane of A431 cells prepared by the quick-freeze deep-etch technique. This image shows coated pits and clathrin-coated vesicles in different stages of their formation. Note that the coated pits and clathrin-coated vesicles are formed in areas devoid of actin flaments. The small uniform pinocytotic vesicles do not have a clathrin coat and are located in close proximity to actin flaments. 200,000. (Courtesy of Dr. John E. Heuser,
Washington University School of Medicine.) immunoglobulins by plasma cells and of procollagen by fibroblasts. This pathway is present to some degree in all cells. The TEM reveals that these cells lack secretory granules.
 In the regulated secretory pathway, specialized cells, such as endocrine and exocrine cells and neurons, concentrate secretory proteins and transiently store them in secretory vesicles within the cytoplasm (Fig. 2.12). In this case, a regulatory event (hormonal or neural stimulus) must be activated for secretion to occur, as in the release of secretory vesicles by chief cells of the gastric mucosa and by acinar cells of the pancreas. The signaling stimulus causes a transient inﬂux of Ca2 into the cytoplasm, which in turn stimulates secretory vesicles to fuse with the plasma membrane and discharge their contents (Fig. 2.13). In the past, secretory vesicle containing inactive precursor (zymogen) were called zymogen granules.
In addition to excretory pathways, proteins can be transported between the Golgi apparatus and other organelles along endosomal pathways. These pathways are used for delivery of organelle-specific proteins, such as lysosomal structural proteins, into the appropriate organelles.
The precise targeting of vesicles to the appropriate cellular compartment is initially controlled by docking proteins, and specificity is ensured by interactions between soluble NSF attachment receptor (SNARE) proteins.