Moving and positioning the endolysosomal system

Abstract

The endolysosomal system is extremely dynamic, yet highly organized. The spatio-temporal distribution of endolysosomal organelles depends on transport driven by microtubule motors such as kinesins and dynein, and by actin-based myosin motors. It has recently become appreciated that interactions with motors are controlled by contacts with other organelles, particularly the endoplasmic reticulum (ER). The ER also controls the concentration of endolysosomal organelles in the perinuclear area, as well as their fission and fusion, through a complex system of tethering proteins. Dynamic interactions go both ways, as contacts with endosomes can influence the movement of the ER and peroxisomes. The dynamics of endolysosomal organelles should thus no longer be studied in isolation, but in the context of the whole endomembrane system.

Figure 1

Microtubule-dependent transport of endolysosomal organelles. This cartoon depicts different endolysosomal organelles and the microtubule motors and adaptors that drive their movement. EE, early endosome; RE, recycling endosome; LE, late endosome; Lys, lysosome; Mel, melanosome; LG, lytic granule; MTOC, microtubule-organizing center. The minus (−) and plus (+) ends of microtubules are indicated. Arrows indicate the direction of movement driven by the corresponding motor-adaptor combinations. Notice that whereas in most cells the MTOC is located near the cell center, in activated cytotoxic T lymphocytes (CTL) it is relocated to an area under the immunological synapse. See Table 1 for references.

Figure 2

Contacts of LEs/lysosomes with the ER and Golgi complex. Schematic representation of interactions between LEs/lysosomes and other organelles. The multiple interactions with the ER often involve the ER protein VAP (A and B isoforms). These interactions control the overall positioning of the LEs/lysosomes, their association with kinesin and dynein motors, and their fission and fusion with other organelles. Also depicted are interactions of LEs/lysosomes with the Golgi complex. See Table 2 for references.