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The EMBO Journal Oct 2014The last decade has been marked by tremendous progress in our understanding of the cell biology of mitochondria, with the identification of molecules and mechanisms that... (Review)
Review
The last decade has been marked by tremendous progress in our understanding of the cell biology of mitochondria, with the identification of molecules and mechanisms that regulate their fusion, fission, motility, and the architectural transitions within the inner membrane. More importantly, the manipulation of these machineries in tissues has provided links between mitochondrial dynamics and physiology. Indeed, just as the proteins required for fusion and fission were identified, they were quickly linked to both rare and common human diseases. This highlighted the critical importance of this emerging field to medicine, with new hopes of finding drugable targets for numerous pathologies, from neurodegenerative diseases to inflammation and cancer. In the midst of these exciting new discoveries, an unexpected new aspect of mitochondrial cell biology has been uncovered; the generation of small vesicular carriers that transport mitochondrial proteins and lipids to other intracellular organelles. These mitochondrial-derived vesicles (MDVs) were first found to transport a mitochondrial outer membrane protein MAPL to a subpopulation of peroxisomes. However, other MDVs did not target peroxisomes and instead fused with the late endosome, or multivesicular body. The Parkinson's disease-associated proteins Vps35, Parkin, and PINK1 are involved in the biogenesis of a subset of these MDVs, linking this novel trafficking pathway to human disease. In this review, we outline what has been learned about the mechanisms and functional importance of MDV transport and speculate on the greater impact of these pathways in cellular physiology.
Topics: Animals; Humans; Mitochondria; Mitochondrial Proteins; Organelles; Transport Vesicles
PubMed: 25107473
DOI: 10.15252/embj.201488104 -
Cellular and Molecular Life Sciences :... Sep 2015Microtubule-based distribution of organelles/vesicles is crucial for the function of many types of eukaryotic cells and the molecular motor cytoplasmic dynein is... (Review)
Review
Microtubule-based distribution of organelles/vesicles is crucial for the function of many types of eukaryotic cells and the molecular motor cytoplasmic dynein is required for transporting a variety of cellular cargos toward the microtubule minus ends. Early endosomes represent a major cargo of dynein in filamentous fungi, and dynein regulators such as LIS1 and the dynactin complex are both required for early endosome movement. In fungal hyphae, kinesin-3 and dynein drive bi-directional movements of early endosomes. Dynein accumulates at microtubule plus ends; this accumulation depends on kinesin-1 and dynactin, and it is important for early endosome movements towards the microtubule minus ends. The physical interaction between dynein and early endosome requires the dynactin complex, and in particular, its p25 component. The FTS-Hook-FHIP (FHF) complex links dynein-dynactin to early endosomes, and within the FHF complex, Hook interacts with dynein-dynactin, and Hook-early endosome interaction depends on FHIP and FTS.
Topics: Biological Transport; Cytoplasm; Dyneins; Endosomes; Fungi; Microtubules; Models, Biological
PubMed: 26001903
DOI: 10.1007/s00018-015-1926-y -
Cold Spring Harbor Perspectives in... Aug 2011Receptor-mediated endocytosis is used by a number of viruses and toxins to gain entry into cells. Some have evolved to use specific lipids in the plasma membrane as... (Review)
Review
Receptor-mediated endocytosis is used by a number of viruses and toxins to gain entry into cells. Some have evolved to use specific lipids in the plasma membrane as their receptors. They include bacterial toxins such as Shiga and Cholera toxin and viruses such as mouse polyoma virus and simian virus 40. Through multivalent binding to glycosphingolipids, they induce lipid clustering and changes in membrane properties. Internalization occurs by unusual endocytic mechanisms involving lipid rafts, induction of membrane curvature, trans-bilayer coupling, and activation of signaling pathways. Once delivered to early endosomes, they follow diverse intracellular routes to the lumen of the ER, from which they penetrate into the cytosol. The role of the lipid receptors is central in these well-studied processes.
Topics: Animals; Bacterial Toxins; Clathrin; Endocytosis; Glycosphingolipids; Humans; Ligands; Membrane Microdomains; Transport Vesicles; Virus Attachment; Virus Internalization
PubMed: 21576253
DOI: 10.1101/cshperspect.a004721 -
Autophagy Mar 2022Selective autophagy of damaged organelles assures maintenance of cellular homeostasis in eukaryotes. While the mechanisms by which cells selectively remove dysfunctional...
Selective autophagy of damaged organelles assures maintenance of cellular homeostasis in eukaryotes. While the mechanisms by which cells selectively remove dysfunctional mitochondria, lysosomes, endoplasmic reticulum and other organelles has been well characterized, little is known about specific autophagy of damaged early endosomes. In our recent study, we uncovered a new role for RABEP1/Rabaptin5, a long-established regulator of early endosome function, in targeting the autophagy machinery to early endosomes damaged by chloroquine or by internalized via interaction with RB1CC1/FIP200 and ATG16L1.
Topics: Autophagy; Autophagy-Related Proteins; Endosomes; Homeostasis; Transport Vesicles
PubMed: 35000547
DOI: 10.1080/15548627.2021.2021497 -
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 -
Cold Spring Harbor Perspectives in... Mar 2018The delivery of intracellular material within cells is crucial for maintaining normal function. Myosins transport a wide variety of cargo, ranging from vesicles to... (Review)
Review
The delivery of intracellular material within cells is crucial for maintaining normal function. Myosins transport a wide variety of cargo, ranging from vesicles to ribonuclear protein particles (RNPs), in plants, fungi, and metazoa. The properties of a given myosin transporter are adapted to move on different actin filament tracks, either on the disordered actin networks at the cell cortex or along highly organized actin bundles to distribute their cargo in a localized manner or move it across long distances in the cell. Transport is controlled by selective recruitment of the myosin to its cargo that also plays a role in activation of the motor.
Topics: Animals; Biological Transport; Cytoplasmic Streaming; Humans; Myosins; Organelles; Plants; RNA; Ribonucleoproteins; Secretory Vesicles; Transport Vesicles
PubMed: 29496823
DOI: 10.1101/cshperspect.a021972 -
The Biochemical Journal Feb 2022Membrane traffic in eukaryotic cells is mediated by transport vesicles that bud from a precursor compartment and are transported to their destination compartment where... (Review)
Review
Membrane traffic in eukaryotic cells is mediated by transport vesicles that bud from a precursor compartment and are transported to their destination compartment where they dock and fuse. To reach their intracellular destination, transport vesicles contain targeting signals such as Rab GTPases and polyphosphoinositides that are recognized by tethering factors in the cytoplasm and that connect the vesicles with their respective destination compartment. The final step, membrane fusion, is mediated by SNARE proteins. SNAREs are connected to targeting signals and tethering factors by multiple interactions. However, it is still debated whether SNAREs only function downstream of targeting and tethering or whether they also participate in regulating targeting specificity. Here, we review the evidence and discuss recent data supporting a role of SNARE proteins as targeting signals in vesicle traffic.
Topics: Cell Membrane; Eukaryotic Cells; Humans; Membrane Fusion; Protein Transport; SNARE Proteins; Signal Transduction; Transport Vesicles; rab GTP-Binding Proteins
PubMed: 35119456
DOI: 10.1042/BCJ20210719 -
Methods in Molecular Biology (Clifton,... 2015Rab proteins represent the largest branch of the Ras-like small GTPase superfamily and there are 66 Rab genes in the human genome. They alternate between GTP- and... (Review)
Review
Rab proteins represent the largest branch of the Ras-like small GTPase superfamily and there are 66 Rab genes in the human genome. They alternate between GTP- and GDP-bound states, which are facilitated by guanine nucleotide exchange factors (GEFs) and GTPase-activating proteins (GAPs), and function as molecular switches in regulation of intracellular membrane trafficking in all eukaryotic cells. Each Rab targets to an organelle and specify a transport step along exocytic, endocytic, and recycling pathways as well as the crosstalk between these pathways. Through interactions with multiple effectors temporally, a Rab can control membrane budding and formation of transport vesicles, vesicle movement along cytoskeleton, and membrane fusion at the target compartment. The large number of Rab proteins reflects the complexity of the intracellular transport system, which is essential for the localization and function of membrane and secretory proteins such as hormones, growth factors, and their membrane receptors. As such, Rab proteins have emerged as important regulators for signal transduction, cell growth, and differentiation. Altered Rab expression and/or activity have been implicated in diseases ranging from neurological disorders, diabetes to cancer.
Topics: Animals; Biological Transport; Humans; Transport Vesicles; rab GTP-Binding Proteins
PubMed: 25800828
DOI: 10.1007/978-1-4939-2569-8_1 -
The Journal of Cell Biology Mar 2021We have long known that lipids traffic between cellular membranes via vesicles but have only recently appreciated the role of nonvesicular lipid transport. Nonvesicular... (Review)
Review
We have long known that lipids traffic between cellular membranes via vesicles but have only recently appreciated the role of nonvesicular lipid transport. Nonvesicular transport can be high volume, supporting biogenesis of rapidly expanding membranes, or more targeted and precise, allowing cells to rapidly alter levels of specific lipids in membranes. Most such transport probably occurs at membrane contact sites, where organelles are closely apposed, and requires lipid transport proteins (LTPs), which solubilize lipids to shield them from the aqueous phase during their transport between membranes. Some LTPs are cup like and shuttle lipid monomers between membranes. Others form conduits allowing lipid flow between membranes. This review describes what we know about nonvesicular lipid transfer mechanisms while also identifying many remaining unknowns: How do LTPs facilitate lipid movement from and into membranes, do LTPs require accessory proteins for efficient transfer in vivo, and how is directionality of transport determined?
Topics: Animals; Biological Transport; Humans; Lipid Metabolism; Models, Biological; Mutation; Transport Vesicles
PubMed: 33605998
DOI: 10.1083/jcb.202012058 -
Biomolecules Aug 2020Carbohydrate-binding galectins are expressed in various tissues of multicellular organisms. They are involved in autophagy, cell migration, immune response,... (Review)
Review
Carbohydrate-binding galectins are expressed in various tissues of multicellular organisms. They are involved in autophagy, cell migration, immune response, inflammation, intracellular transport, and signaling. In recent years, novel roles of galectin-interaction with membrane components have been characterized, which lead to the formation of vesicles with diverse functions. These vesicles are part of intracellular transport pathways, belong to the cellular degradation machinery, or can be released for cell-to-cell communication. Several characteristics of galectins in the lumen or at the membrane of newly formed vesicular structures are discussed in this review and illustrate the need to fully elucidate their contributions at the molecular and structural level.
Topics: Animals; Biological Transport, Active; Cell Communication; Cytoplasmic Vesicles; Exosomes; Extracellular Vesicles; Galectins; Humans; Models, Biological; Signal Transduction; Transport Vesicles
PubMed: 32847140
DOI: 10.3390/biom10091232