Moving and positioning the endolysosomal system

Abstract

The endolysosomal system is extremely dynamic, yet highly organized. The spatiotemporal 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.

Whole-Cell Scale Dynamic Organization of Lysosomes Revealed by Spatial Statistical Analysis

“…Because microtubule-based active transport is crucial to the positioning and relocation of lysosomes (Bonifacino and Neefjes, 2017; Pu et al, 2016), we reason that it should play an important role in maintaining the stable spatial distributions of lysosomes. To test this hypothesis, we compared the three distance distributions of the lysosomes right before and 30 min after the nocodazole treatment (Figure 2F).…”

“…This raises the question of what maintains the sub-population undergoing constrained diffusion. Interaction of lysosomes with the actin cytoskeleton plays an important role in mediating their positioning (Bonifacino and Neefjes, 2017; Pu et al, 2016). In particular, interaction with the cortical actin network has been shown to transiently constrain lysosomes near the cell periphery (Caviston et al, 2011; Encarnação et al, 2016).…”

“…The number of lysosomes in a mammalian cell typically is limited to several hundred (Valm et al, 2017). Furthermore, lysosomes are specialized compartments that depend on interactions with partner organelles to fulfill their functions (Bonifacino and Neefjes, 2017; Luzio et al, 2007). For example, they depend on fusion with endosomes and autophagosomes to receive and degrade materials from the endocytic and autophagic pathways, respectively (Eskelinen and Saftig, 2009; Luzio et al, 2007).…”

“…Recent studies on the positioning of lysosomes (Bonifacino and Neefjes, 2017; Pu et al, 2016) have begun to reveal their spatial organization within the intracellular space. Positioning of individual lysosomes is mediated by mechanisms that include their active transport along microtubules and their interactions with the actin cytoskeleton and partner organelles, especially the ER (Bonifacino and Neefjes, 2017; Pu et al, 2016; Valm et al, 2017).…”

“…Positioning of individual lysosomes is mediated by mechanisms that include their active transport along microtubules and their interactions with the actin cytoskeleton and partner organelles, especially the ER (Bonifacino and Neefjes, 2017; Pu et al, 2016; Valm et al, 2017). Under normal conditions, lysosomes in non-polarized mammalian cells often cluster in a perinuclear region surrounding the microtubule-organizing center (MTOC), forming what is called the perinuclear cloud (Jongsma et al, 2016; Korolchuk et al, 2011; Pu et al, 2016), but they also spread into peripheral regions of cells, with some approaching the plasma membrane.…”