How early endosomes arise is not entirely clear, but their membrane and volume are mainly derived from incoming endocytic vesicles that fuse with one another (Movie 13.4). Early endosomes are relatively small and patrol the cytoplasm underlying the plasma membrane in jerky back-and-forth movements along microtubules, capturing incoming vesicles. Typically, an early endosome receives incoming vesicles for about 10 minutes, during which time membrane and fluid is rapidly recycled to the plasma membrane. Some of the incoming cargo, however, accumulates over the lifetime of the early endosome, eventually to be included in the late endosome.
0.5 µm
Figure 13–53 Electron micrograph of an early endosome. The endosome is labeled with endocytosed horseradish peroxidase, a widely used enzyme marker, detected in this case by an electron-dense reaction product. Many tubular extensions protrude from the central vacuolar space of the  early endosome, which will later mature  to give rise to a late endosome. (from
J. Tooze and M. hollinshead, J. Cell Biol. 118:813–830, 1992.)
Early endosomes have tubular and vacuolar domains (see Figure 13–53). Most of the membrane surface is in the tubules and most of the volume is in the vacuolar domain. During endosome maturation, the two domains have different fates: the vacuolar portions of the early endosome are retained and transformed into late endosomes; the tubular portions shrink. Maturing endosomes, also called multivesicular bodies, migrate along microtubules toward the cell interior, shedding membrane tubules and vesicles that recycle material to the plasma membrane and TGN, and receiving newly synthesized lysosomal proteins. As they concentrate in a perinuclear region of the cell, the multivesicular bodies fuse with each other, and eventually with endolysosomes and lysosomes (see Figure 13–47).
Many changes occur during the maturation process. (1) The endosome changes shape and location, as the tubular domains are lost and the vacuolar domains are thoroughly modified. (2) Rab proteins, phosphoinositide lipids, fusion machinery (SNAREs and tethers), and microtubule motor proteins all participate in a molecular makeover of the cytosolic face of the endosome membrane, changing the functional characteristics of the organelle. (3) A V-type ATPase in the endosome membrane pumps H+ from the cytosol into the endosome lumen and acidifies the organelle. Crucially, the increasing acidity that accompanies maturation renders lysosomal hydrolases increasingly more active, influencing many receptor–ligand interactions, thereby controlling receptor loading and unloading. (4) Intralumenal vesicles sequester endocytosed signaling receptors inside the endosome, thus halting the receptor signaling activity. (5) Lysosome proteins are delivered from the TGN to the maturing endosome. Most of these events occur gradually but eventually lead to a complete transformation of the endosome into an early endolysosome.
In addition to committing selected cargo for degradation, the maturation process is important for lysosome maintenance. The continual delivery of lysosome components from the TGN to maturing endosomes, ensures a steady supply of new lysosome proteins. The endocytosed materials mix in early endosomes with newly arrived acid hydrolases. Although mild digestion may start here, many hydrolases are synthesized and delivered as proenzymes, called zymogens, which contain extra inhibitory domains that keep the hydrolases inactive until these domains are proteolytically removed at later stages of endosome maturation. Moreover, the pH in early endosomes is not low enough to activate lysosomal hydrolases optimally. By these means, cells can retrieve membrane proteins intact from early endosomes and recycle them back to the plasma membrane.