The Endosomal Network: Mediators and Regulators of Endosome Maturation

Abstract

Endocytosis is a means for the cell to sample its environment for nutrients and regulate plasma membrane (PM) composition and area. Whereas the majority of internalized cargo is recycled back to the cell surface, select material is sent to the lysosome for degradation. Endosomes further play major roles in central cell activities as diverse as establishment of cell polarity and signaling, lysosomal storage and immunity. The complexity of endosomal functions is reflected by the extensive changes to endosome properties as they mature. The identity of individual endosomes is influenced by the presence of specific Rab GTPases and phosphoinositides (PIPs), which coordinate membrane traffic and facilitate endosomal functions. Motors and tethers direct the endosomes to the required locations and moderate fusion with other organelles. The maintenance of the elaborate endosomal network is supported by the ER and the trans-Golgi network (TGN), which promote the exchange of membrane components, provide enzymes, and assist with signaling. Additionally, V-ATPase is emerging as an underappreciated coordinator of endosome maturation and cell signaling. The inputs of the various mediators of endosome maturation are tightly regulated and coordinated to ensure appropriate maintenance and functioning of endosomes at each stage of the maturation process. Perturbations in endosome maturation are implicated in devastating diseases, such as neurodegeneration and cancer, and the endosome maturation processes are manipulated and exploited by intracellular pathogens to meet their own needs. A greater understanding of coordination and fine-tuning of endosome maturation will help us address various pathologies more effectively.

PDZD8 interacts with Protrudin and Rab7 at ER-late endosome membrane contact sites associated with mitochondria

“…The early to late endosome maturation process consists of an intertwined complex series of steps, which include endosomal acidification, a Rab5 to Rab7 switch, an interdependent conversion of membrane PIP from PI(3)P to PI(3,5)P2 and an alteration of the lipid composition as late endosomes become depleted in phosphatidylserine (PS) and rich in the unique phospholipid lysobisphosphatidic acid (LBPA) 31 – 33 . To gain insight into what endosomal maturation stage the PDZD8-mediated ER-late endosome MCS forms, we co-expressed in U2OS cells PDZD8-GFP and BFP-Rab7 with either mCherry-Rab5 or LAMP1-mCherry.…”

PEDV enters cells through clathrin-, caveolae-, and lipid raft-mediated endocytosis and traffics via the endo-/lysosome pathway

“…Late endosomes can become larger vesicles by fusing with the same type of endosomes, so they mostly exist in the form of a multivesicular body (MVB). Late endosomes release Rab5, incorporate Rab7, and prepare to fuse with lysosomes [62]. To explore whether PEDV particles are trafficked after internalization, we interfered with the expression of Rab7 [63] involved in late endosomes and VPS39 [32] involved in late endosometo-lysosome maturation and identified whether viral particles co-located with early endosomes, late endosomes and lysosomes.…”

The Role of Secretory Pathways in Candida albicans Pathogenesis

“…Exosomes are formed and transported as part of the endosomal network and are released upon fusion of multivesicular bodies with the plasma membrane [24,25]. The ER and the trans-Golgi network reinforce the preservation of the endosomal network, which promotes the exchange of membrane components, provide enzymes, and assist with signaling [26]. Transport mechanisms for both exocytosis and endocytosis are complex and use partially overlapping protein complexes that facilitate these processes.…”