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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 -
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 -
Journal of Cell Science Jan 2020Microtubules are part of the dynamic cytoskeleton network and composed of tubulin dimers. They are the main tracks used in cells to organize organelle positioning and... (Review)
Review
Microtubules are part of the dynamic cytoskeleton network and composed of tubulin dimers. They are the main tracks used in cells to organize organelle positioning and trafficking of cargos. In this Review, we compile recent findings on the involvement of microtubules in anterograde protein transport. First, we highlight the importance of microtubules in organelle positioning. Second, we discuss the involvement of microtubules within different trafficking steps, in particular between the endoplasmic reticulum and the Golgi complex, traffic through the Golgi complex itself and in post-Golgi processes. A large number of studies have assessed the involvement of microtubules in transport of cargo from the Golgi complex to the cell surface. We focus here on the role of kinesin motor proteins and protein interactions in post-Golgi transport, as well as the impact of tubulin post-translational modifications. Last, in light of recent findings, we highlight the role microtubules have in exocytosis, the final step of secretory protein transport, occurring close to focal adhesions.
Topics: Humans; Microtubules; Protein Transport
PubMed: 31996399
DOI: 10.1242/jcs.237016 -
Molecular and Cellular Neurosciences Jun 2023The extreme length of neuronal processes poses a challenge for synapse-to-nucleus communication. In response to this challenge several different mechanisms have evolved... (Review)
Review
The extreme length of neuronal processes poses a challenge for synapse-to-nucleus communication. In response to this challenge several different mechanisms have evolved in neurons to couple synaptic activity to the regulation of gene expression. One of these mechanisms concerns the long-distance transport of proteins from pre- and postsynaptic sites to the nucleus. In this review we summarize current evidence on mechanisms of transport and consequences of nuclear import of these proteins for gene transcription. In addition, we discuss how information from pre- and postsynaptic sites might be relayed to the nucleus by this type of long-distance signaling. When applicable, we highlight how long-distance protein transport from synapse-to-nucleus can provide insight into the pathophysiology of disease or reveal new opportunities for therapeutic intervention.
Topics: Protein Transport; Cell Nucleus; Synapses; Active Transport, Cell Nucleus; Neurons
PubMed: 37084990
DOI: 10.1016/j.mcn.2023.103854 -
Seminars in Cell & Developmental Biology Apr 2018Mitochondria are fundamental structures that fulfil important and diverse functions within cells, including cellular respiration and iron-sulfur cluster biogenesis.... (Review)
Review
Mitochondria are fundamental structures that fulfil important and diverse functions within cells, including cellular respiration and iron-sulfur cluster biogenesis. Mitochondrial function is reliant on the organelles proteome, which is maintained and adjusted depending on cellular requirements. The majority of mitochondrial proteins are encoded by nuclear genes and must be trafficked to, and imported into the organelle following synthesis in the cytosol. These nuclear-encoded mitochondrial precursors utilise dynamic and multimeric translocation machines to traverse the organelles membranes and be partitioned to the appropriate mitochondrial subcompartment. Yeast model systems have been instrumental in establishing the molecular basis of mitochondrial protein import machines and mechanisms, however unique players and mechanisms are apparent in higher eukaryotes. Here, we review our current knowledge on mitochondrial protein import in human cells and how dysfunction in these pathways can lead to disease.
Topics: Humans; Mitochondrial Proteins; Protein Transport
PubMed: 28765093
DOI: 10.1016/j.semcdb.2017.07.028 -
Open Biology Aug 2023Encapsulation and compartmentalization are fundamental to the evolution of cellular life, but they also pose a challenge: how to partition the molecules that perform... (Review)
Review
Encapsulation and compartmentalization are fundamental to the evolution of cellular life, but they also pose a challenge: how to partition the molecules that perform biological functions-the proteins-across impermeable barriers into sub-cellular organelles, and to the outside. The solution lies in the evolution of specialized machines, translocons, found in every biological membrane, which act both as gate and gatekeeper across and into membrane bilayers. Understanding how these translocons operate at the molecular level has been a long-standing ambition of cell biology, and one that is approaching its denouement; particularly in the case of the ubiquitous Sec system. In this review, we highlight the fruits of recent game-changing technical innovations in structural biology, biophysics and biochemistry to present a largely complete mechanism for the bacterial version of the core Sec machinery. We discuss the merits of our model over alternative proposals and identify the remaining open questions. The template laid out by the study of the Sec system will be of immense value for probing the many other translocons found in diverse biological membranes, towards the ultimate goal of altering or impeding their functions for pharmaceutical or biotechnological purposes.
Topics: Protein Transport; Cell Membrane
PubMed: 37643640
DOI: 10.1098/rsob.230166 -
Annual Review of Cell and Developmental... 2015One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best-studied... (Review)
Review
One of the major challenges in biology is to explain how complex tissues and organs arise from the collective action of individual polarized cells. The best-studied model of this process is the cross talk between individual epithelial cells during their polarization to form the multicellular epithelial lumen during tissue morphogenesis. Multiple mechanisms of apical lumen formation have been proposed. Some epithelial lumens form from preexisting polarized epithelial structures. However, de novo lumen formation from nonpolarized cells has recently emerged as an important driver of epithelial tissue morphogenesis, especially during the formation of small epithelial tubule networks. In this review, we discuss the latest findings regarding the mechanisms and regulation of de novo lumen formation in vitro and in vivo.
Topics: Animals; Cell Polarity; Epithelial Cells; Humans; Morphogenesis; Protein Transport
PubMed: 26359775
DOI: 10.1146/annurev-cellbio-100814-125323 -
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 -
Essays in Biochemistry 2000Transport along the secretory pathway is largely signal-mediated. Proteins in the secretory pathway can be covalently modified with various carbohydrate structures, most... (Review)
Review
Transport along the secretory pathway is largely signal-mediated. Proteins in the secretory pathway can be covalently modified with various carbohydrate structures, most commonly O-glycans, N-glycans and/or proteoglycans. Carbohydrate modifications can change the physical properties of proteins or can function as specific recognition epitopes. Glycosylation can act as an apical sorting signal in polarized epithelial cells and provide a signal for surface transport in non-polarized fibroblasts. Homologues of leguminous plant lectins have been identified in yeast, fruitflies, worms and humans. Intracellular lectins are candidate receptors in the secretory pathway to mediate concentration of cargo in carrier vesicles.
Topics: Animals; Cell Polarity; Glycoproteins; Glycosylation; Golgi Apparatus; Humans; Protein Transport
PubMed: 12471900
DOI: 10.1042/bse0360027 -
The FEBS Journal Mar 2009
Topics: Animals; Humans; Organelles; Protein Transport
PubMed: 19187237
DOI: 10.1111/j.1742-4658.2009.06872.x