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Seminars in Cell & Developmental Biology Jul 2014Efficient sorting of the material internalized by endocytosis is essential for key cellular functions and represents a, if not the, major trafficking pathway in... (Review)
Review
Efficient sorting of the material internalized by endocytosis is essential for key cellular functions and represents a, if not the, major trafficking pathway in mammalian cells. Incoming material - solutes, receptors and cargos, lipids and even pathogenic agents - are routed to various destinations within mammalian cells at two major sorting stations: the early and late endosome. The early endosome receives all manner of incoming material from the plasma membrane, as well as from the Golgi, and serves as an initial sorting nexus routing molecules back to the cell surface through recycling endosomes, to the trans-Golgi network by retrograde transport, or on to the late endosome/lysosome. The early endosome also regulates cell signaling, through the downregulation of internalized receptors, which are packaged into intralumenal vesicles that arise from inward invaginations of the limiting membrane. These multivesicular regions detach or mature from early endosomes and become free endocytic carrier vesicle/multivesicular body, which transports cargoes to late endosomes. The late endosome provides a central hub for incoming traffic from the endocytic, biosynthetic and autophagic pathways and outgoing traffic to the lysosomes, the Golgi complex or the plasma membrane. They also function as a key sensing/signaling platform that inform the cell about the nutrient situation. Herein we summarize the current understanding of the organization and functions of the endocytic pathway, differences across species, and the process of endosome maturation.
Topics: Animals; Biological Transport; Endosomes; Humans
PubMed: 24709024
DOI: 10.1016/j.semcdb.2014.03.034 -
Trends in Cell Biology Nov 2018Eukaryotic cells maintain a highly organized endolysosomal system. This system regulates the protein and lipid content of the plasma membrane, it participates in the... (Review)
Review
Eukaryotic cells maintain a highly organized endolysosomal system. This system regulates the protein and lipid content of the plasma membrane, it participates in the intracellular quality control machinery and is needed for the efficient removal of damaged organelles. This complex network comprises an endosomal membrane system that feeds into the lysosomes, yet also allows recycling of membrane proteins, and probably lipids. Moreover, lysosomal degradation provides the cell with macromolecules for further growth. In this review, we focus primarily on the role of the small Rab GTPases Rab5 and Rab7 as organelle markers and interactors of multiple effectors on endosomes and lysosomes and highlight their role in membrane dynamics, particularly fusion along the endolysosomal pathway.
Topics: Biomarkers; Endosomes; Humans; Lysosomes; rab GTP-Binding Proteins
PubMed: 30025982
DOI: 10.1016/j.tcb.2018.06.007 -
Current Opinion in Cell Biology Feb 2023The plasma membrane (PM) and its associated cargo are internalized into small vesicles via endocytosis funneling cargo into endosomes. The endosomal system must... (Review)
Review
The plasma membrane (PM) and its associated cargo are internalized into small vesicles via endocytosis funneling cargo into endosomes. The endosomal system must efficiently deliver cargos, as well as recycle cargo receptors and membrane to maintain homeostasis. In animal cells, endosome trafficking, maturation, and cargo recycling rely on the actin and microtubule cytoskeleton. Microtubules and their associated motor proteins provide the roads on which endosomes move and fuse during cargo sorting and delivery. In addition, highly dynamic assemblies of actin adjust the shape of the endosomal membrane to promote cargo segregation into budding domains allowing for receptor recycling. Recent work has revealed that the endoplasmic reticulum (ER) frequently acts as an intermediary between endosomes and their cytoskeletal regulators via membrane contact sites (MCSs). This review will discuss the factors which form these tripartite junction between the ER, endosomes, and the cytoskeleton as well as their function.
Topics: Animals; Actins; Endosomes; Microtubules; Cytoskeleton; Endocytosis; Protein Transport; Endoplasmic Reticulum
PubMed: 36848759
DOI: 10.1016/j.ceb.2023.102155 -
Annals of Neurology Jul 2021Intracellular protein trafficking via the endosomes plays a key role in the maintenance of normal neuronal function. Although many diseases of the central nervous system... (Review)
Review
Intracellular protein trafficking via the endosomes plays a key role in the maintenance of normal neuronal function. Although many diseases of the central nervous system exhibit specific pathological hallmarks, abnormalities of the endosome system are common traits for several of them, including Alzheimer disease (AD). Three main routes originate from the endosomes: the recycling, degradation, and retrograde pathways. Studies have shown that the majority of Down syndrome subjects develop AD pathology and manifest altered morphology and number of endosomes, and abnormalities in lysosome acidification and exosome secretion, suggesting that dysfunction of one of these pathways could play a functional role in the AD-like phenotype of the syndrome. Two of the major endosomal routes are mediated by the retromer complex, a multimeric system responsible for transport of cargo from the endosome to the trans-Golgi network or to the cell membrane. Recently, a new endosome system structurally related to the retromer, called "retriever," has been reported. Whereas we know a great deal about the neuropathophysiology of the retromer complex, no precise pathogenic role for the retriever has yet been identified. Here, we will review the neurobiology of the endosome system and its role as key player in the development of AD-like pathology in Down syndrome. Additionally, we will discuss current knowledge on these two main endosome systems, retromer and retriever, and their potential as novel therapeutic targets. ANN NEUROL 2021;90:4-14.
Topics: Alzheimer Disease; Animals; Brain; Down Syndrome; Endosomes; Humans; trans-Golgi Network
PubMed: 33547827
DOI: 10.1002/ana.26042 -
Traffic (Copenhagen, Denmark) Jan 2020The late endosomes/endo-lysosomes of vertebrates contain an atypical phospholipid, lysobisphosphatidic acid (LBPA) (also termed bis[monoacylglycero]phosphate [BMP]),... (Review)
Review
The late endosomes/endo-lysosomes of vertebrates contain an atypical phospholipid, lysobisphosphatidic acid (LBPA) (also termed bis[monoacylglycero]phosphate [BMP]), which is not detected elsewhere in the cell. LBPA is abundant in the membrane system present in the lumen of this compartment, including intralumenal vesicles (ILVs). In this review, the current knowledge on LBPA and LBPA-containing membranes will be summarized, and their role in the control of endosomal cholesterol will be outlined. Some speculations will also be made on how this system may be overwhelmed in the cholesterol storage disorder Niemann-Pick C. Then, the roles of intralumenal membranes in endo-lysosomal dynamics and functions will be discussed in broader terms. Likewise, the mechanisms that drive the biogenesis of intralumenal membranes, including ESCRTs, will also be discussed, as well as their diverse composition and fate, including degradation in lysosomes and secretion as exosomes. This review will also discuss how intralumenal membranes are hijacked by pathogenic agents during intoxication and infection, and what is the biochemical composition and function of the intra-endosomal lumenal milieu. Finally, this review will allude to the size limitations imposed on intralumenal vesicle functions and speculate on the possible role of LBPA as calcium chelator in the acidic calcium stores of endo-lysosomes.
Topics: Animals; Cholesterol; Endocytosis; Endosomes; Lysophospholipids; Lysosomes; Multivesicular Bodies
PubMed: 31854087
DOI: 10.1111/tra.12715 -
Journal of Controlled Release :... Jul 2021Non-viral vehicles hold therapeutic promise in advancing the delivery of a variety of cargos in vitro and in vivo, including small molecule drugs, biologics, and... (Review)
Review
Non-viral vehicles hold therapeutic promise in advancing the delivery of a variety of cargos in vitro and in vivo, including small molecule drugs, biologics, and especially nucleic acids. However, their efficacy at the cellular level is limited by several delivery barriers, with endolysosomal degradation being most significant. The entrapment of vehicles and their cargo in the acidified endosome prevents access to the cytosol, nucleus, and other subcellular compartments. Understanding the factors that contribute to uptake and intracellular trafficking, especially endosomal entrapment and release, is key to overcoming delivery obstacles within cells. In this review, we summarize and compare experimental techniques for assessing the extent of endosomal escape of a variety of non-viral vehicles and describe proposed escape mechanisms for different classes of lipid-, polymer-, and peptide-based delivery agents. Based on this evaluation, we present forward-looking strategies utilizing information gained from mechanistic studies to inform the rational design of efficient delivery vehicles.
Topics: Cytosol; Endosomes; Lysosomes; Peptides; Polymers
PubMed: 34077782
DOI: 10.1016/j.jconrel.2021.05.038 -
Journal of Cell Science Jul 2018The early endosome (EE), also known as the sorting endosome (SE) is a crucial station for the sorting of cargoes, such as receptors and lipids, through the endocytic... (Review)
Review
The early endosome (EE), also known as the sorting endosome (SE) is a crucial station for the sorting of cargoes, such as receptors and lipids, through the endocytic pathways. The term endosome relates to the receptacle-like nature of this organelle, to which endocytosed cargoes are funneled upon internalization from the plasma membrane. Having been delivered by the fusion of internalized vesicles with the EE or SE, cargo molecules are then sorted to a variety of endocytic pathways, including the endo-lysosomal pathway for degradation, direct or rapid recycling to the plasma membrane, and to a slower recycling pathway that involves a specialized form of endosome known as a recycling endosome (RE), often localized to the perinuclear endocytic recycling compartment (ERC). It is striking that 'the endosome', which plays such essential cellular roles, has managed to avoid a precise description, and its characteristics remain ambiguous and heterogeneous. Moreover, despite the rapid advances in scientific methodologies, including breakthroughs in light microscopy, overall, the endosome remains poorly defined. This Review will attempt to collate key characteristics of the different types of endosomes and provide a platform for discussion of this unique and fascinating collection of organelles. Moreover, under-developed, poorly understood and important open questions will be discussed.
Topics: Animals; Biological Transport; Endocytosis; Endosomes; Humans; Transport Vesicles
PubMed: 29980602
DOI: 10.1242/jcs.216499 -
European Journal of Cell Biology Mar 2017Retrograde passage of a transport carrier entails cargo sorting at the endosome, generation of a cargo-laden carrier and its movement along cytoskeletal tracks towards... (Review)
Review
Retrograde passage of a transport carrier entails cargo sorting at the endosome, generation of a cargo-laden carrier and its movement along cytoskeletal tracks towards trans-Golgi network (TGN), tethering at the TGN, and fusion with the Golgi membrane. Significant advances have been made in understanding this traffic system, revealing molecular requirements in each step and the functional connection between them as well as biomedical implication of the dysregulation of those important traffic factors. This review focuses on describing up-to-date action mechanisms for retrograde transport from the endosomal system to the TGN.
Topics: Endosomes; Humans; trans-Golgi Network
PubMed: 28256269
DOI: 10.1016/j.ejcb.2017.02.005 -
Cellular and Molecular Life Sciences :... Sep 2015Sorting of macromolecules within the endosomal system is vital for physiological control of nutrient homeostasis, cell motility, and proteostasis. Trafficking routes... (Review)
Review
Sorting of macromolecules within the endosomal system is vital for physiological control of nutrient homeostasis, cell motility, and proteostasis. Trafficking routes that export macromolecules from the endosome via vesicle and tubule transport carriers constitute plasma membrane recycling and retrograde endosome-to-Golgi pathways. Proteins of the sorting nexin family have been discovered to function at nearly every step of endosomal transport carrier biogenesis and it is becoming increasingly clear that they form the core machineries of cargo-specific transport pathways that are closely integrated with cellular physiology. Here, we summarize recent progress in elucidating the pathways that mediate the biogenesis of endosome-derived transport carriers.
Topics: Biological Transport; Cell Membrane; Endosomes; Golgi Apparatus; Humans; Vesicular Transport Proteins
PubMed: 26022064
DOI: 10.1007/s00018-015-1935-x -
Biochemical Society Transactions Jun 2008In mammalian cells, completion of cytokinesis relies on targeted delivery of recycling membranes to the midbody. At this step of mitosis, recycling endosomes are... (Review)
Review
In mammalian cells, completion of cytokinesis relies on targeted delivery of recycling membranes to the midbody. At this step of mitosis, recycling endosomes are organized as clusters located at the mitotic spindle poles as well as at both sides of the midbody. However, the mechanism that controls endosome positioning during cytokinesis is not known. Here, we discuss the possible mechanisms that drive the formation of endosomal clusters and the importance of this process for the targeted delivery of recycling membranes to the midbody.
Topics: Animals; Biological Transport; Cell Membrane; Cytokinesis; Endosomes; Microtubules
PubMed: 18481977
DOI: 10.1042/BST0360442