scholarly journals The emerging role of sorting nexins in cardiovascular diseases

2019 ◽  
Vol 133 (5) ◽  
pp. 723-737 ◽  
Author(s):  
Jian Yang ◽  
Van Anthony M. Villar ◽  
Selim Rozyyev ◽  
Pedro A. Jose ◽  
Chunyu Zeng
Keyword(s):  
Protein Trafficking ◽  
Current Knowledge ◽  
Endocytic Pathway ◽  
Regulatory Mechanisms ◽  
Diverse Group ◽  
Sorting Nexins ◽  
Endosomal Sorting ◽  
Sorting Nexin ◽  
Endosomal Signaling

AbstractThe sorting nexin (SNX) family consists of a diverse group of cytoplasmic- and membrane-associated phosphoinositide-binding proteins that play pivotal roles in the regulation of protein trafficking. This includes the entire endocytic pathway, such as endocytosis, endosomal sorting, and endosomal signaling. Dysfunctions of SNX pathway are involved in several forms of cardiovascular disease (CVD). Moreover, SNX gene variants are associated with CVDs. In this review, we discuss the current knowledge on SNX-mediated regulatory mechanisms and their roles in the pathogenesis and treatment of CVDs.

scholarly journals HIV Assembly and Budding: Ca2+ Signaling and Non-ESCRT Proteins Set the Stage

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Lorna S. Ehrlich ◽  
Carol A. Carter
Keyword(s):  
Protein Trafficking ◽  
Endocytic Pathway ◽  
Host Proteins ◽  
Virus Budding ◽  
Endosomal Sorting ◽  
The Past ◽  
Escrt Machinery ◽  
Cellular Factors ◽  
Hiv 1

More than a decade has elapsed since the link between the endosomal sorting complex required for transport (ESCRT) machinery and HIV-1 protein trafficking and budding was first identified. L domains in HIV-1 Gag mediate recruitment of ESCRT which function in bud abscission releasing the viral particle from the host cell. Beyond virus budding, the ESCRT machinery is also involved in the endocytic pathway, cytokinesis, and autophagy. In the past few years, the number of non-ESCRT host proteins shown to be required in the assembly process has also grown. In this paper, we highlight the role of recently identified cellular factors that link ESCRT machinery to calcium signaling machinery and we suggest that this liaison contributes to setting the stage for productive ESCRT recruitment and mediation of abscission. Parallel paradigms for non-ESCRT roles in virus budding and cytokinesis will be discussed.

Protein trafficking to plastids: one theme, many variations

2008 ◽  
Vol 413 (1) ◽  
pp. 15-28 ◽  
Author(s):  
Takehito Inaba ◽  
Danny J. Schnell
Keyword(s):  
Gene Expression ◽  
Plant Development ◽  
Protein Trafficking ◽  
Protein Import ◽  
Current Knowledge ◽  
Regulatory Mechanisms ◽  
Diverse Group ◽  
Double Membrane ◽  
Plastid Envelope ◽  
Plastid Protein

Plastids are a diverse group of essential organelles in plants that include chloroplasts. The biogenesis and maintenance of these organelles relies on the import of thousands of nucleus-encoded proteins. The complexity of plastid structure has resulted in the evolution of at least four general import pathways that target proteins into and across the double membrane of the plastid envelope. Several of these pathways can be further divided into specialty pathways that mediate and regulate the import of specific classes of proteins. The co-ordination of import by these specialized pathways with changes in gene expression is critical for plastid and plant development. Moreover, protein import is acutely regulated in response to physiological and metabolic changes within the cell. In the present review we summarize the current knowledge of the mechanism of import via these pathways and highlight the regulatory mechanisms that integrate the plastid protein-trafficking pathways with the developmental and metabolic state of the plant.

scholarly journals Sequence-dependent cargo recognition by SNX-BARs mediates retromer-independent transport of CI-MPR

2017 ◽  
Vol 216 (11) ◽  
pp. 3695-3712 ◽  
Author(s):  
Boris Simonetti ◽  
Chris M. Danson ◽  
Kate J. Heesom ◽  
Peter J. Cullen
Keyword(s):  
Transmembrane Proteins ◽  
Endosomal Sorting ◽  
Sorting Nexin ◽  
Sequence Dependent ◽  
Endosomal Recycling ◽  
Cytosolic Domains ◽  
Sorting Motif ◽  
Golgi Network ◽  
Coupling Sequence

Endosomal recycling of transmembrane proteins requires sequence-dependent recognition of motifs present within their intracellular cytosolic domains. In this study, we have reexamined the role of retromer in the sequence-dependent endosome-to–trans-Golgi network (TGN) transport of the cation-independent mannose 6-phosphate receptor (CI-MPR). Although the knockdown or knockout of retromer does not perturb CI-MPR transport, the targeting of the retromer-linked sorting nexin (SNX)–Bin, Amphiphysin, and Rvs (BAR) proteins leads to a pronounced defect in CI-MPR endosome-to-TGN transport. The retromer-linked SNX-BAR proteins comprise heterodimeric combinations of SNX1 or SNX2 with SNX5 or SNX6 and serve to regulate the biogenesis of tubular endosomal sorting profiles. We establish that SNX5 and SNX6 associate with the CI-MPR through recognition of a specific WLM endosome-to-TGN sorting motif. From validating the CI-MPR dependency of SNX1/2–SNX5/6 tubular profile formation, we provide a mechanism for coupling sequence-dependent cargo recognition with the biogenesis of tubular profiles required for endosome-to-TGN transport. Therefore, the data presented in this study reappraise retromer’s role in CI-MPR transport.

scholarly journals Proteasome Inhibitors Block a Late Step in Lysosomal Transport of Selected Membrane but not Soluble Proteins

2001 ◽  
Vol 12 (8) ◽  
pp. 2556-2566 ◽  
Author(s):  
Peter van Kerkhof ◽  
Cristina M. Alves dos Santos ◽  
Martin Sachse ◽  
Judith Klumperman ◽  
Guojun Bu ◽  
...  
Keyword(s):  
Membrane Proteins ◽  
Proteasome Inhibitors ◽  
Endocytic Pathway ◽  
Endosomal Sorting ◽  
Ubiquitin Proteasome Pathway ◽  
Late Step ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
Lysosomal Transport

The ubiquitin-proteasome pathway acts as a regulator of the endocytosis of selected membrane proteins. Recent evidence suggests that it may also function in the intracellular trafficking of membrane proteins. In this study, several models were used to address the role of the ubiquitin-proteasome pathway in sorting of internalized proteins to the lysosome. We found that lysosomal degradation of ligands, which remain bound to their receptors within the endocytic pathway, is blocked in the presence of specific proteasome inhibitors. In contrast, a ligand that dissociates from its receptor upon endosome acidification is degraded under the same conditions. Quantitative electron microscopy showed that neither the uptake nor the overall distribution of the endocytic marker bovine serum albumin-gold is substantially altered in the presence of a proteasome inhibitor. The data suggest that the ubiquitin-proteasome pathway is involved in an endosomal sorting step of selected membrane proteins to lysosomes, thereby providing a mechanism for regulated degradation.

ESCRT-mediated sorting and intralumenal vesicle concatenation in plants

2018 ◽  
Vol 46 (3) ◽  
pp. 537-545 ◽  
Author(s):  
Marisa S. Otegui
Keyword(s):  
Plasma Membrane ◽  
Membrane Proteins ◽  
Endocytic Pathway ◽  
Endosomal Sorting ◽  
Evolutionary Diversification ◽  
Escrt Machinery ◽  
Membrane Fission ◽  
Associated Proteins

The degradation of plasma membrane and other membrane-associated proteins require their sorting at endosomes for delivery to the vacuole. Through the endocytic pathway, ubiquitinated membrane proteins (cargo) are delivered to endosomes where the ESCRT (endosomal sorting complex required for transport) machinery sorts them into intralumenal vesicles for degradation. Plants contain both conserved and plant-specific ESCRT subunits. In this review, I discuss the role of characterized plant ESCRT components, the evolutionary diversification of the plant ESCRT machinery, and a recent study showing that endosomal intralumenal vesicles form in clusters of concatenated vesicle buds by temporally uncoupling membrane constriction from membrane fission.

Retromer and sorting nexins in endosomal sorting

2015 ◽  
Vol 43 (1) ◽  
pp. 33-47 ◽  
Author(s):  
Matthew Gallon ◽  
Peter J. Cullen
Keyword(s):  
Plasma Membrane ◽  
Present Article ◽  
Transmembrane Proteins ◽  
Molecular Architecture ◽  
Sorting Nexins ◽  
Endosomal Sorting ◽  
Sorting Nexin ◽  
Cargo Proteins ◽  
Associated Proteins ◽  
Lysosome Related Organelles

The evolutionarily conserved endosomal retromer complex rescues transmembrane proteins from the lysosomal degradative pathway and facilitates their recycling to other cellular compartments. Retromer functions in conjunction with numerous associated proteins, including select members of the sorting nexin (SNX) family. In the present article, we review the molecular architecture and cellular roles of retromer and its various functional partners. The endosomal network is a crucial hub in the trafficking of proteins through the cellular endomembrane system. Transmembrane proteins, here termed cargos, enter endosomes by endocytosis from the plasma membrane or by trafficking from the trans-Golgi network (TGN). Endosomal cargo proteins face one of the two fates: retention in the endosome, leading ultimately to lysosomal degradation or export from the endosome for reuse (‘recycling’). The balance of protein degradation and recycling is crucial to cellular homoeostasis; inappropriate sorting of proteins to either fate leads to cellular dysfunction. Retromer is an endosome-membrane-associated protein complex central to the recycling of many cargo proteins from endosomes, both to the TGN and the plasma membrane (and other specialized compartments, e.g. lysosome-related organelles). Retromer function is reliant on a number of proteins from the SNX family. In the present article, we discuss this inter-relationship and how defects in retromer function are increasingly being linked with human disease.

Endocytic Rabs in membrane trafficking and signaling

2014 ◽  
Vol 395 (3) ◽  
pp. 327-333 ◽  
Author(s):  
Johannes Numrich ◽  
Christian Ungermann
Keyword(s):  
Signal Transduction ◽  
Plasma Membrane ◽  
Membrane Trafficking ◽  
Current Knowledge ◽  
Cell Stress ◽  
Endocytic Pathway ◽  
Rab Gtpases ◽  
Endosomal Membranes ◽  
Amino Acid Sensing

Abstract The endolysosomal system controls the trafficking of proteins between the plasma membrane and the degradative environment of the lysosome. The early endosomal Rab5 and the late endosomal Rab7 GTPases have a key role in the transport along the endocytic pathway by recruiting tethering factors such as the hexameric CORVET and HOPS complexes that promote membrane fusion. Both Rabs are also involved in signaling at endosomal membranes and linked to amino acid sensing and autophagy, indicating that their role in trafficking may be connected to signal transduction and adaptation during cell stress. Here, we will summarize the current knowledge on the role of both Rab GTPases on both processes and discuss the possible crosstalk between them.

scholarly journals Regulation of peroxisomal trafficking and distribution

2020 ◽  
Author(s):  
Christian Covill-Cooke ◽  
Viktoriya S. Toncheva ◽  
Josef T. Kittler
Keyword(s):  
Rho Gtpases ◽  
Mammalian Cells ◽  
Short Range ◽  
Current Knowledge ◽  
Current Understanding ◽  
Regulatory Mechanisms ◽  
Future Directions ◽  
Contact Sites ◽  
Wide Range

Abstract Peroxisomes are organelles that perform a wide range of essential metabolic processes. To ensure that peroxisomes are optimally positioned in the cell, they must be transported by both long- and short-range trafficking events in response to cellular needs. Here, we review our current understanding of the mechanisms by which the cytoskeleton and organelle contact sites alter peroxisomal distribution. Though the focus of the review is peroxisomal transport in mammalian cells, findings from flies and fungi are used for comparison and to inform the gaps in our understanding. Attention is given to the apparent overlap in regulatory mechanisms for mitochondrial and peroxisomal trafficking, along with the recently discovered role of the mitochondrial Rho-GTPases, Miro, in peroxisomal dynamics. Moreover, we outline and discuss the known pathological and pharmacological conditions that perturb peroxisomal positioning. We conclude by highlighting several gaps in our current knowledge and suggest future directions that require attention.

scholarly journals Molecular Basis of Inflammation in the Pathogenesis of Cardiomyopathies

2020 ◽  
Vol 21 (18) ◽  
pp. 6462
Author(s):  
Emanuele Monda ◽  
Giuseppe Palmiero ◽  
Marta Rubino ◽  
Federica Verrillo ◽  
Federica Amodio ◽  
...  
Keyword(s):  
Molecular Basis ◽  
Molecular Mechanisms ◽  
Current Knowledge ◽  
Molecular Targets ◽  
Diverse Group ◽  
Myocardial Diseases ◽  
Immune System Activation ◽  
System Activation ◽  
Sarcomeric Genes

Cardiomyopathies (CMPs) represent a diverse group of heart muscle diseases, grouped into specific morphological and functional phenotypes. CMPs are associated with mutations in sarcomeric and non-sarcomeric genes, with several suspected epigenetic and environmental mechanisms involved in determining penetrance and expressivity. The understanding of the underlying molecular mechanisms of myocardial diseases is fundamental to achieving a proper management and treatment of these disorders. Among these, inflammation seems to play an important role in the pathogenesis of CMPs. The aim of the present study is to review the current knowledge on the role of inflammation and the immune system activation in the pathogenesis of CMPs and to identify potential molecular targets for a tailored anti-inflammatory treatment.

scholarly journals Current Knowledge on the Multifactorial Regulation of Corpora Lutea Lifespan: The Rabbit Model

Animals ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. 296
Author(s):  
Massimo Zerani ◽  
Angela Polisca ◽  
Cristiano Boiti ◽  
Margherita Maranesi
Keyword(s):  
Regulatory Mechanism ◽  
Current Knowledge ◽  
Mammalian Species ◽  
Rabbit Model ◽  
Regulatory Mechanisms ◽  
Corpora Lutea ◽  
Healthy Pregnancy ◽  
Gonadotrophin Releasing Hormone ◽  
Efficient Breeding

Our research group studied the biological regulatory mechanisms of the corpora lutea (CL), paying particular attention to the pseudopregnant rabbit model, which has the advantage that the relative luteal age following ovulation is induced by the gonadotrophin-releasing hormone (GnRH). CL are temporary endocrine structures that secrete progesterone, which is essential for maintaining a healthy pregnancy. It is now clear that, besides the classical regulatory mechanism exerted by prostaglandin E2 (luteotropic) and prostaglandin F2 (luteolytic), a considerable number of other effectors assist in the regulation of CL. The aim of this paper is to summarize our current knowledge of the multifactorial mechanisms regulating CL lifespan in rabbits. Given the essential role of CL in reproductive success, a deeper understanding of the regulatory mechanisms will provide us with valuable insights on various reproductive issues that hinder fertility in this and other mammalian species, allowing to overcome the challenges for new and more efficient breeding strategies.

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