scholarly journals Nuclear transport of cancer extracellular vesicle-derived biomaterials through nuclear envelope invagination-associated late endosomes

Oncotarget ◽  
2017 ◽  
Vol 8 (9) ◽  
pp. 14443-14461 ◽  
Author(s):  
Germana Rappa ◽  
Mark F. Santos ◽  
Toni M. Green ◽  
Jana Karbanová ◽  
Justin Hassler ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Transport ◽  
Extracellular Vesicle ◽  
Late Endosomes

scholarly journals Author response: An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system

2019 ◽  
Author(s):  
David J Thaller ◽  
Matteo Allegretti ◽  
Sapan Borah ◽  
Paolo Ronchi ◽  
Martin Beck ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Transport System ◽  
Surveillance System ◽  
Nuclear Transport ◽  
Author Response

scholarly journals Nuclear Envelope and Nuclear Pore Complexes in Neurodegenerative Diseases—New Perspectives for Therapeutic Interventions

2020 ◽  
Author(s):  
Naomi Hachiya ◽  
Marta Sochocka ◽  
Anna Brzecka ◽  
Takuto Shimizu ◽  
Kazimierz Gąsiorowski ◽  
...  
Keyword(s):  
Gene Expression ◽  
Neurodegenerative Diseases ◽  
Nuclear Envelope ◽  
Neurodegenerative Disorders ◽  
Nuclear Transport ◽  
Therapeutic Interventions ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Pore Complexes ◽  
Bidirectional Exchange

Abstract Transport of proteins, transcription factors, and other signaling molecules between the nucleus and cytoplasm is necessary for signal transduction. The study of these transport phenomena is particularly challenging in neurons because of their highly polarized structure. The bidirectional exchange of molecular cargoes across the nuclear envelope (NE) occurs through nuclear pore complexes (NPCs), which are aqueous channels embedded in the nuclear envelope. The NE and NPCs regulate nuclear transport but are also emerging as relevant regulators of chromatin organization and gene expression. The alterations in nuclear transport are regularly identified in affected neurons associated with human neurodegenerative diseases. This review presents insights into the roles played by nuclear transport defects in neurodegenerative disease, focusing primarily on NE proteins and NPCs. The subcellular mislocalization of proteins might be a very desirable means of therapeutic intervention in neurodegenerative disorders.

scholarly journals Brl1p - A Novel Nuclear Envelope Protein Required for Nuclear Transport

Traffic ◽  
2005 ◽  
Vol 6 (6) ◽  
pp. 502-517 ◽  
Author(s):  
Yoh-hei Saitoh ◽  
Kaoru Ogawa ◽  
Takeharu Nishimoto
Keyword(s):  
Nuclear Envelope ◽  
Envelope Protein ◽  
Nuclear Transport

scholarly journals Nuclear envelope-vacuole contacts mitigate nuclear pore complex assembly stress

2020 ◽  
Author(s):  
Christopher L. Lord ◽  
Susan R. Wente
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Nuclear Envelope ◽  
Nuclear Pore Complex ◽  
Lipid Droplets ◽  
Budding Yeast ◽  
Nuclear Transport ◽  
Nuclear Pore ◽  
Cellular Mechanisms ◽  
Complex Assembly ◽  
Cellular Effects

AbstractThe intricacy of nuclear pore complex (NPC) biogenesis imposes risks of failure that can cause defects in nuclear transport and nuclear envelope morphology, however, cellular mechanisms utilized to alleviate NPC assembly stress are not well-defined. In the budding yeast Saccharomyces cerevisiae, we demonstrate that NVJ1- and MDM1-enriched nuclear envelope (NE)-vacuole contacts increase when NPC assembly is compromised in several nup mutants, including nup116ΔGLFG cells. These interorganelle nucleus-vacuole junctions (NVJs) cooperate with lipid droplets to maintain viability and enhance NPC formation in assembly mutants. Additionally, NVJs function with ATG1 to promote vacuole-dependent remodeling in nup116ΔGLFG cells, which also correlates with proper NPC formation. Importantly, NVJs significantly improve the physiology of NPC assembly mutants, despite having only negligible effects when NPC biogenesis is unperturbed. Collectively, these results define how NE-vacuole interorganelle contacts coordinate responses to mitigate deleterious cellular effects caused by disrupted NPC assembly.SummaryHow cells respond to deleterious effects imposed by disrupted nuclear pore complex (NPC) assembly are not well-defined. The authors demonstrate nuclear envelope-vacuole interactions expand in response to perturbed NPC assembly to promote viability, nuclear envelope remodeling, and proper NPC biogenesis.

scholarly journals Role of the RAB7 Protein in Tumor Progression and Cisplatin Chemoresistance

Cancers ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 1096 ◽  
Author(s):  
Guerra ◽  
Bucci
Keyword(s):  
Cancer Progression ◽  
Extracellular Vesicle ◽  
Endocytic Pathway ◽  
Cellular Processes ◽  
Molecular Events ◽  
Late Endosomes ◽  
Early Endosomes ◽  
Cellular Context ◽  
Guanosine Triphosphatase

RAB7 is a small guanosine triphosphatase (GTPase) extensively studied as regulator of vesicular trafficking. Indeed, its role is fundamental in several steps of the late endocytic pathway, including endosome maturation, transport from early endosomes to late endosomes and lysosomes, clustering and fusion of late endosomes and lysosomes in the perinuclear region and lysosomal biogenesis. Besides endocytosis, RAB7 is important for a number of other cellular processes among which, autophagy, apoptosis, signaling, and cell migration. Given the importance of RAB7 in these cellular processes, the interest to study the role of RAB7 in cancer progression is widely grown. Here, we describe the current understanding of oncogenic and oncosuppressor functions of RAB7 analyzing cellular context and other environmental factors in which it elicits pro and/or antitumorigenic effects. We also discuss the role of RAB7 in cisplatin resistance associated with its ability to regulate the late endosomal pathway, lysosomal biogenesis and extracellular vesicle secretion. Finally, we examined the potential cancer therapeutic strategies targeting the different molecular events in which RAB7 is involved.

scholarly journals Nuclear transport defects and nuclear envelope alterations are associated with mutation of the Saccharomyces cerevisiae NPL4 gene.

1996 ◽  
Vol 7 (11) ◽  
pp. 1835-1855 ◽  
Author(s):  
C DeHoratius ◽  
P A Silver
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Pore Complex ◽  
Protein Import ◽  
Nuclear Protein ◽  
Nuclear Transport ◽  
Nuclear Pore ◽  
Temperature Sensitive ◽  
Nonpermissive Temperature ◽  
Temperature Sensitive Mutants ◽  
Nuclear Protein Import

To identify components involved in nuclear protein import, we used a genetic selection to isolate mutants that mislocalized a nuclear-targeted protein. We identified temperature-sensitive mutants that accumulated several different nuclear proteins in the cytoplasm when shifted to the semipermissive temperature of 30 degrees C; these were termed npl (nuclear protein localization) mutants. We now present the properties of yeast strains bearing mutations in the NPL4 gene and report the cloning of the NPL4 gene and the characterization of the Np14 protein. The npl4-1 mutant was isolated by the previously described selection scheme. The second allele, npl4-2, was identified from an independently derived collection of temperature-sensitive mutants. The npl4-1 and npl4-2 strains accumulate nuclear-targeted proteins in the cytoplasm at the nonpermissive temperature consistent with a defect in nuclear protein import. Using an in vitro nuclear import assay, we show that nuclei prepared from temperature-shifted npl4 mutant cells are unable to import nuclear-targeted proteins, even in the presence of cytosol prepared from wild-type cells. In addition, npl4-2 cells accumulate poly(A)+ RNA in the nucleus at the nonpermissive temperature, consistent with a failure to export mRNA from the nucleus. The npl4-1 and npl4-2 cells also exhibit distinct, temperature-sensitive structural defects: npl4-1 cells project extra nuclear envelope into the cytoplasm, whereas npl4-2 cells from nuclear envelope herniations that appear to be filled with poly(A)+ RNA. The NPL4 gene encodes an essential M(r) 64,000 protein that is located at the nuclear periphery and localizes in a pattern similar to nuclear pore complex proteins. Taken together, these results indicate that this gene encodes a novel nuclear pore complex or nuclear pore complex-associated component required for nuclear membrane integrity and nuclear transport.

scholarly journals An ESCRT-LEM protein surveillance system is poised to directly monitor the nuclear envelope and nuclear transport system

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
David J Thaller ◽  
Matteo Allegretti ◽  
Sapan Borah ◽  
Paolo Ronchi ◽  
Martin Beck ◽  
...  
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Membrane ◽  
Surveillance System ◽  
Nuclear Transport ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Nuclear Membranes ◽  
Disease Mechanisms ◽  
Pore Complexes ◽  
Membrane Sealing

The integrity of the nuclear membranes coupled to the selective barrier of nuclear pore complexes (NPCs) are essential for the segregation of nucleoplasm and cytoplasm. Mechanical membrane disruption or perturbation to NPC assembly triggers an ESCRT-dependent surveillance system that seals nuclear pores: how these pores are sensed and sealed is ill defined. Using a budding yeast model, we show that the ESCRT Chm7 and the integral inner nuclear membrane (INM) protein Heh1 are spatially segregated by nuclear transport, with Chm7 being actively exported by Xpo1/Crm1. Thus, the exposure of the INM triggers surveillance with Heh1 locally activating Chm7. Sites of Chm7 hyperactivation show fenestrated sheets at the INM and potential membrane delivery at sites of nuclear envelope herniation. Our data suggest that perturbation to the nuclear envelope barrier would lead to local nuclear membrane remodeling to promote membrane sealing. Our findings have implications for disease mechanisms linked to NPC assembly and nuclear envelope integrity.

Nucleocytoplasmic transport of macromolecules

1997 ◽  
Vol 61 (2) ◽  
pp. 193-211
Author(s):  
A H Corbett ◽  
P A Silver
Keyword(s):  
Nuclear Envelope ◽  
Nuclear Transport ◽  
Bound State ◽  
Nucleocytoplasmic Transport ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Yeast Saccharomyces Cerevisiae ◽  
Soluble Factors ◽  
Pore Complexes ◽  
Transport Of Macromolecules

Nucleocytoplasmic transport is a complex process that consists of the movement of numerous macromolecules back and forth across the nuclear envelope. All macromolecules that move in and out of the nucleus do so via nuclear pore complexes that form large proteinaceous channels in the nuclear envelope. In addition to nuclear pores, nuclear transport of macromolecules requires a number of soluble factors that are found both in the cytoplasm and in the nucleus. A combination of biochemical, genetic, and cell biological approaches have been used to identify and characterize the various components of the nuclear transport machinery. Recent studies have shown that both import to and export from the nucleus are mediated by signals found within the transport substrates. Several studies have demonstrated that these signals are recognized by soluble factors that target these substrates to the nuclear pore. Once substrates have been directed to the pore, most transport events depend on a cycle of GTP hydrolysis mediated by the small Ras-like GTPase, Ran, as well as other proteins that regulate the guanine nucleotide-bound state of Ran. Many of the essential factors have been identified, and the challenge that remains is to determine the exact mechanism by which transport occurs. This review attempts to present an integrated view of our current understanding of nuclear transport while highlighting the contributions that have been made through studies with genetic organisms such as the budding yeast, Saccharomyces cerevisiae.

scholarly journals Itraconazole inhibits nuclear delivery of extracellular vesicle cargo by disrupting the entry of late endosomes into the nucleoplasmic reticulum

2021 ◽  
Vol 10 (10) ◽  
Author(s):  
Mark F. Santos ◽  
Germana Rappa ◽  
Jana Karbanová ◽  
Simona Fontana ◽  
Maria Antonietta Di Bella ◽  
...  
Keyword(s):  
Extracellular Vesicle ◽  
Late Endosomes ◽  
Nucleoplasmic Reticulum
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