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Current Biology : CB Nov 2017Mitochondria are best known for their role in the generation of ATP by aerobic respiration. Yet, research in the past half century has shown that they perform a much... (Review)
Review
Mitochondria are best known for their role in the generation of ATP by aerobic respiration. Yet, research in the past half century has shown that they perform a much larger suite of functions and that these functions can vary substantially among diverse eukaryotic lineages. Despite this diversity, all mitochondria derive from a common ancestral organelle that originated from the integration of an endosymbiotic alphaproteobacterium into a host cell related to Asgard Archaea. The transition from endosymbiotic bacterium to permanent organelle entailed a massive number of evolutionary changes including the origins of hundreds of new genes and a protein import system, insertion of membrane transporters, integration of metabolism and reproduction, genome reduction, endosymbiotic gene transfer, lateral gene transfer and the retargeting of proteins. These changes occurred incrementally as the endosymbiont and the host became integrated. Although many insights into this transition have been gained, controversy persists regarding the nature of the original endosymbiont, its initial interactions with the host and the timing of its integration relative to the origin of other features of eukaryote cells. Since the establishment of the organelle, proteins have been gained, lost, transferred and retargeted as mitochondria have specialized into the spectrum of functional types seen across the eukaryotic tree of life.
Topics: Adenosine Triphosphate; Alphaproteobacteria; Biological Evolution; Eukaryotic Cells; Genome, Mitochondrial; Membrane Transport Proteins; Mitochondria; Protein Transport; Symbiosis
PubMed: 29112874
DOI: 10.1016/j.cub.2017.09.015 -
Microbiological Research Oct 2019T. gondii is a major opportunistic pathogen chronically infecting nearly one third of the world's population. Due to the high infection and mortality rates in... (Review)
Review
T. gondii is a major opportunistic pathogen chronically infecting nearly one third of the world's population. Due to the high infection and mortality rates in immunocompromised patients and newborns, the extent or magnitude of T. gondii pathogenesis is determined mainly by host-pathogen interactions. T. gondii utilizes specialized secretory proteins to modify host cellular factors and facilitate invasion and replication. This review provides update on the recent progress in this field of research with particular emphasis on the T. gondii secretory proteins and their role in invasion and pathogenesis.
Topics: Animals; Host-Parasite Interactions; Humans; Life Cycle Stages; Protein Transport; Protozoan Proteins; Toxoplasma; Toxoplasmosis
PubMed: 31421715
DOI: 10.1016/j.micres.2019.06.003 -
The Journal of Cell Biology Mar 2019Palade's corpus placed small vesicles as the sole means to transport proteins across stable distinct compartments of the secretory pathway. We suggest that cargo,... (Review)
Review
Palade's corpus placed small vesicles as the sole means to transport proteins across stable distinct compartments of the secretory pathway. We suggest that cargo, spatial organization of secretory compartments, and the timing of fission of cargo-filled containers dictate the design of transport intermediates that can be vesicles and transient direct tunnels.
Topics: Animals; Golgi Apparatus; Humans; Protein Transport; Secretory Pathway; Transport Vesicles
PubMed: 30718263
DOI: 10.1083/jcb.201811073 -
Traffic (Copenhagen, Denmark) May 2017Cilia and eukaryotic flagella are threadlike cell extensions with motile and sensory functions. Their assembly requires intraflagellar transport (IFT), a bidirectional... (Review)
Review
Cilia and eukaryotic flagella are threadlike cell extensions with motile and sensory functions. Their assembly requires intraflagellar transport (IFT), a bidirectional motor-driven transport of protein carriers along the axonemal microtubules. IFT moves ample amounts of structural proteins including tubulin into growing cilia likely explaining its critical role for assembly. IFT continues in non-growing cilia contributing to a variety of processes ranging from axonemal maintenance and the export of non-ciliary proteins to cell locomotion and ciliary signaling. Here, we discuss recent data on cues regulating the type, amount and timing of cargo transported by IFT. A regulation of IFT-cargo interactions is critical to establish, maintain and adjust ciliary length, protein composition and function.
Topics: Animals; Cilia; Flagella; Humans; Protein Transport; Proteins; Tubulin
PubMed: 28248449
DOI: 10.1111/tra.12474 -
Autophagy Apr 2023The endosomal system maintains cellular homeostasis by coordinating multiple vesicular trafficking events, and the retromer complex plays a critical role in endosomal...
The endosomal system maintains cellular homeostasis by coordinating multiple vesicular trafficking events, and the retromer complex plays a critical role in endosomal cargo recognition and sorting. Here, we demonstrate an essential role for the small GTPase RAB21 in regulating retromer-mediated recycling of the glucose transporter SLC2A1/GLUT1 and macroautophagy/autophagy. RAB21 depletion mis-sorts SLC2A1 to lysosomes and affects glucose uptake, thereby activating the AMPK-ULK1 pathway to increase autophagic flux. RAB21 depletion also increases lysosome function. Notably, RAB21 depletion does not overtly affect retrograde transport of IGF2R/CI-M6PR or WLS from endosomes to the trans-Golgi network. We speculate that RAB21 regulates fission of retromer-decorated endosomal tubules, as RAB21 depletion causes accumulation of the SNX27-containing retromer complex on enlarged endosomes at the perinuclear region. Functionally, RAB21 depletion sensitizes cancer cells to energy stress and inhibits tumor growth in vivo, suggesting an oncogenic role for RAB21. Overall, our study illuminates the role of RAB21 in regulating endosomal dynamics and maintaining cellular energy homeostasis and suggests RAB21 as a potential metabolic target for cancer therapy.
Topics: Vesicular Transport Proteins; Autophagy; Glucose Transporter Type 1; Protein Transport; Endosomes; Homeostasis
PubMed: 35993307
DOI: 10.1080/15548627.2022.2114271 -
Molecular Plant Aug 2021Drought is the leading environmental threat affecting crop productivity, and plants have evolved a series of mechanisms to adapt to drought stress. The FT-interacting...
Drought is the leading environmental threat affecting crop productivity, and plants have evolved a series of mechanisms to adapt to drought stress. The FT-interacting proteins (FTIPs) and phosphatidylethanolamine-binding proteins (PEBPs) play key roles in developmental processes, whereas their roles in the regulation of stress response are still largely unknown. Here, we report that OsFTIP1 negatively regulates drought response in rice. We showed that OsFTIP1 interacts with rice MOTHER OF FT AND TFL1 (OsMFT1), a PEBP that promotes rice tolerance to drought treatment. Further studies discovered that OsMFT1 interacts with two key drought-related transcription factors, OsbZIP66 and OsMYB26, regulating their binding capacity on drought-related genes and thereby enhancing drought tolerance in rice. Interestingly, we found that OsFTIP1 impedes the nucleocytoplasmic translocation of OsMFT1, implying that dynamic modulation of drought-responsive genes by the OsMFT1-OsMYB26 and OsMFT1-OsbZIP66 complexes is integral to OsFTIP1-modulated nuclear accumulation of OsMFT1. Our findings also suggest that OsMFT1 might act as a hitherto unknown nucleocytoplasmic trafficking signal that regulates drought tolerance in rice in response to environmental signals.
Topics: Adaptation, Physiological; Droughts; Gene Expression Regulation, Plant; Oryza; Plant Proteins; Plants, Genetically Modified; Protein Transport; Stress, Physiological; Transcription Factors
PubMed: 33962060
DOI: 10.1016/j.molp.2021.05.001 -
Biomolecules Aug 2022The highly conserved molecular chaperone heat shock protein 90 (Hsp90) is well-known for maintaining metastable proteins and mediating various aspects of intracellular... (Review)
Review
The highly conserved molecular chaperone heat shock protein 90 (Hsp90) is well-known for maintaining metastable proteins and mediating various aspects of intracellular protein dynamics. Intriguingly, high-throughput interactome studies suggest that Hsp90 is associated with a variety of other pathways. Here, we will highlight the potential impact of Hsp90 in protein transport. Currently, a limited number of studies have defined a few mechanistic contributions of Hsp90 to protein transport, yet the relevance of hundreds of additional connections between Hsp90 and factors known to aide this process remains unresolved. These interactors broadly support transport pathways including endocytic and exocytic vesicular transport, the transfer of polypeptides across membranes, or unconventional protein secretion. In resolving how Hsp90 contributes to the protein transport process, new therapeutic targets will likely be obtained for the treatment of numerous human health issues, including bacterial infection, cancer metastasis, and neurodegeneration.
Topics: Cytosol; HSP90 Heat-Shock Proteins; Humans; Molecular Chaperones; Protein Transport
PubMed: 36008972
DOI: 10.3390/biom12081077 -
Cells Jan 2022The quality and quantity of membrane proteins are precisely and dynamically maintained through an endosomal recycling process. This endosomal recycling is executed by... (Review)
Review
The quality and quantity of membrane proteins are precisely and dynamically maintained through an endosomal recycling process. This endosomal recycling is executed by two protein complexes: retromer and recently identified retriever. Defects in the function of retromer or retriever cause dysregulation of many membrane proteins and result in several human disorders, including neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Recently, neurodevelopmental disorders caused by pathogenic variants in genes associated with retriever were identified. This review focuses on the two recycling complexes and discuss their biological and developmental roles and the consequences of defects in endosomal recycling, especially in the nervous system. We also discuss future perspectives of a possible relationship of the dysfunction of retromer and retriever with neurodevelopmental disorders.
Topics: Animals; Disease Models, Animal; Endosomes; Humans; Mice; Neurodevelopmental Disorders; Protein Transport
PubMed: 35011709
DOI: 10.3390/cells11010148 -
Bioscience Reports Jul 2014The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport... (Review)
Review
The AP (adaptor protein) complexes are heterotetrameric protein complexes that mediate intracellular membrane trafficking along endocytic and secretory transport pathways. There are five different AP complexes: AP-1, AP-2 and AP-3 are clathrin-associated complexes; whereas AP-4 and AP-5 are not. These five AP complexes localize to different intracellular compartments and mediate membrane trafficking in distinct pathways. They recognize and concentrate cargo proteins into vesicular carriers that mediate transport from a donor membrane to a target organellar membrane. AP complexes play important roles in maintaining the normal physiological function of eukaryotic cells. Dysfunction of AP complexes has been implicated in a variety of inherited disorders, including: MEDNIK (mental retardation, enteropathy, deafness, peripheral neuropathy, ichthyosis and keratodermia) syndrome, Fried syndrome, HPS (Hermansky-Pudlak syndrome) and HSP (hereditary spastic paraplegia).
Topics: Adaptor Proteins, Vesicular Transport; Animals; Humans; Membrane Proteins; Protein Transport
PubMed: 24975939
DOI: 10.1042/BSR20140069 -
Molecular Neurodegeneration Nov 2022The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely... (Review)
Review
The family of VPS10p-Domain (D) receptors comprises five members named SorLA, Sortilin, SorCS1, SorCS2 and SorCS3. While their physiological roles remain incompletely resolved, they have been recognized for their signaling engagements and trafficking abilities, navigating a number of molecules between endosome, Golgi compartments, and the cell surface. Strikingly, recent studies connected all the VPS10p-D receptors to Alzheimer's disease (AD) development. In addition, they have been also associated with diseases comorbid with AD such as diabetes mellitus and major depressive disorder. This systematic review elaborates on genetic, functional, and mechanistic insights into how dysfunction in VPS10p-D receptors may contribute to AD etiology, AD onset diversity, and AD comorbidities. Starting with their functions in controlling cellular trafficking of amyloid precursor protein and the metabolism of the amyloid beta peptide, we present and exemplify how these receptors, despite being structurally similar, regulate various and distinct cellular events involved in AD. This includes a plethora of signaling crosstalks that impact on neuronal survival, neuronal wiring, neuronal polarity, and synaptic plasticity. Signaling activities of the VPS10p-D receptors are especially linked, but not limited to, the regulation of neuronal fitness and apoptosis via their physical interaction with pro- and mature neurotrophins and their receptors. By compiling the functional versatility of VPS10p-D receptors and their interactions with AD-related pathways, we aim to further propel the AD research towards VPS10p-D receptor family, knowledge that may lead to new diagnostic markers and therapeutic strategies for AD patients.
Topics: Humans; Alzheimer Disease; Amyloid beta-Peptides; Depressive Disorder, Major; Protein Transport; Nerve Growth Factors
PubMed: 36397124
DOI: 10.1186/s13024-022-00576-2