scholarly journals RAB11-Mediated Trafficking and Human Cancers: An Updated Review

Biology ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 26
Author(s):  
Elsi Ferro ◽  
Carla Bosia ◽  
Carlo C. Campa
Keyword(s):  
Plasma Membrane ◽  
Normal Cell ◽  
Vesicular Trafficking ◽  
Small Gtpase ◽  
Cell Physiology ◽  
Biological Mechanisms ◽  
Cellular Processes ◽  
Human Cancers ◽  
Toxic Materials ◽  
Dependent Pathway

Many disorders block and subvert basic cellular processes in order to boost their progression. One protein family that is prone to be altered in human cancers is the small GTPase RAB11 family, the master regulator of vesicular trafficking. RAB11 isoforms function as membrane organizers connecting the transport of cargoes towards the plasma membrane with the assembly of autophagic precursors and the generation of cellular protrusions. These processes dramatically impact normal cell physiology and their alteration significantly affects the survival, progression and metastatization as well as the accumulation of toxic materials of cancer cells. In this review, we discuss biological mechanisms ensuring cargo recognition and sorting through a RAB11-dependent pathway, a prerequisite to understand the effect of RAB11 alterations in human cancers.

scholarly journals CD13 tethers the IQGAP1-ARF6-EFA6 complex to the plasma membrane to promote ARF6 activation, β1 integrin recycling, and cell migration

2019 ◽  
Vol 12 (579) ◽  
pp. eaav5938 ◽  
Author(s):  
Mallika Ghosh ◽  
Robin Lo ◽  
Ivan Ivic ◽  
Brian Aguilera ◽  
Veneta Qendro ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cell Migration ◽  
Cell Adhesion ◽  
Cell Attachment ◽  
Leading Edge ◽  
Small Gtpase ◽  
Β1 Integrin ◽  
Recycling Endosomes ◽  
Cellular Processes ◽  
Early Endosomes

Cell attachment to the extracellular matrix (ECM) requires a balance between integrin internalization and recycling to the surface that is mediated by numerous proteins, emphasizing the complexity of these processes. Upon ligand binding in various cells, the β1 integrin is internalized, traffics to early endosomes, and is returned to the plasma membrane through recycling endosomes. This trafficking process depends on the cyclical activation and inactivation of small guanosine triphosphatases (GTPases) by their specific guanine exchange factors (GEFs) and their GTPase-activating proteins (GAPs). In this study, we found that the cell surface antigen CD13, a multifunctional transmembrane molecule that regulates cell-cell adhesion and receptor-mediated endocytosis, also promoted cell migration and colocalized with β1 integrin at sites of cell adhesion and at the leading edge. A lack of CD13 resulted in aberrant trafficking of internalized β1 integrin to late endosomes and its ultimate degradation. Our data indicate that CD13 promoted ARF6 GTPase activity by positioning the ARF6-GEF EFA6 at the cell membrane. In migrating cells, a complex containing phosphorylated CD13, IQGAP1, GTP-bound (active) ARF6, and EFA6 at the leading edge promoted the ARF6 GTPase cycling and cell migration. Together, our findings uncover a role for CD13 in the fundamental cellular processes of receptor recycling, regulation of small GTPase activities, cell-ECM interactions, and cell migration.

scholarly journals Tyrosine kinase signaling in and on the endoplasmic reticulum

2020 ◽  
Vol 48 (1) ◽  
pp. 199-205 ◽  
Author(s):  
Hesso Farhan
Keyword(s):  
Endoplasmic Reticulum ◽  
Plasma Membrane ◽  
Tyrosine Kinase ◽  
Tyrosine Kinases ◽  
Signaling Molecules ◽  
Cell Physiology ◽  
Kinase Signaling ◽  
Tyrosine Kinase Signaling ◽  
Cellular Processes

Tyrosine kinases are signaling molecules that are common to all metazoans and are involved in the regulation of many cellular processes such as proliferation and survival. While most attention has been devoted to tyrosine kinases signaling at the plasma membrane and the cytosol, very little attention has been dedicated to signaling at endomembranes. In this review, I will discuss recent evidence that we obtained on signaling of tyrosine kinases at the surface of the endoplasmic reticulum (ER), as well as in the lumen of this organelle. I will discuss how tyrosine kinase signaling might regulate ER proteostasis and the implication thereof to general cell physiology.

scholarly journals Mechanisms of activation and key roles of SGK3 under physiological conditions and in prostate and breast cancer.

2020 ◽  
Vol 15 ◽  
Author(s):  
Rajesh Basnet ◽  
Buddha Bahadur Basnet
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Normal Cell ◽  
Cancer Development ◽  
Cell Physiology ◽  
Physiological Conditions ◽  
Cellular Processes ◽  
The Status ◽  
Inducible Protein ◽  
Phosphoinositide 3 Kinase

: The serum and glucocorticoid inducible protein kinase (SGK) family signals downstream of phosphoinositide-3-kinase (PI3K) and is made up of three isoforms: SGK1, 2, and 3. respectively, and their activity is dependent on growth factor activation. Among these SGK family one such potential target and less explored enzyme is SGK3. SGK3 regulate a range of basic cellular processes, such as cell proliferation, migration and survival. Thus play an important role in cancer development. These kinase-signaling pathways present both opportunities and challenges for cancer therapy. In this paper, we reviewed the status of SGK3 regulation and its role in normal cell physiology and transformation. In addition, the potential roles of SGK3 signal transduction in breast cancer and prostate cancer are discussed.

scholarly journals Spatial analysis of Cdc42 activity reveals a role for plasma membrane–associated Cdc42 in centrosome regulation

2017 ◽  
Vol 28 (15) ◽  
pp. 2135-2145 ◽  
Author(s):  
Kari A. Herrington ◽  
Andrew L. Trinh ◽  
Carolyn Dang ◽  
Ellen O’Shaughnessy ◽  
Klaus M. Hahn ◽  
...  
Keyword(s):  
Spatial Distribution ◽  
Plasma Membrane ◽  
Spatial Analysis ◽  
Substantial Reduction ◽  
Cell Polarization ◽  
Small Gtpase ◽  
Spatial Control ◽  
Cytoskeletal Organization ◽  
Cellular Processes ◽  
Phasor Analysis

The ability of the small GTPase Cdc42 to regulate diverse cellular processes depends on tight spatial control of its activity. Cdc42 function is best understood at the plasma membrane (PM), where it regulates cytoskeletal organization and cell polarization. Active Cdc42 has also been detected at the Golgi, but its role and regulation at this organelle are only partially understood. Here we analyze the spatial distribution of Cdc42 activity by moni­toring the dynamics of the Cdc42 FLARE biosensor using the phasor approach to FLIM-FRET. Phasor analysis revealed that Cdc42 is active at all Golgi cisternae and that this activity is controlled by Tuba and ARHGAP10, two Golgi-associated Cdc42 regulators. To our surprise, FGD1, another Cdc42 GEF at the Golgi, was not required for Cdc42 regulation at the Golgi, although its depletion decreased Cdc42 activity at the PM. Similarly, changes in Golgi morphology did not affect Cdc42 activity at the Golgi but were associated with a substantial reduction in PM-associated Cdc42 activity. Of interest, cells with reduced Cdc42 activity at the PM displayed altered centrosome morphology, suggesting that centrosome regulation may be mediated by active Cdc42 at the PM. Our study describes a novel quantitative approach to determine Cdc42 activity at specific subcellular locations and reveals new regulatory principles and functions of this small GTPase.

scholarly journals Consequences of the constitutive NOX2 activity in living cells: cytosol acidification, apoptosis, and localized lipid peroxidation

2021 ◽  
Author(s):  
Hana Valenta ◽  
Sophie Dupré-Crochet ◽  
Tania Bizouarn ◽  
Laura Baciou ◽  
Oliver Nüsse ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Nadph Oxidase ◽  
Living Cells ◽  
Small Gtpase ◽  
Activation Mechanism ◽  
Cell Physiology ◽  
List Type ◽  
Catalytic Core ◽  
Cytosolic Proteins ◽  
Phagocyte Nadph Oxidase

ABSTRACTThe phagocyte NADPH oxidase (NOX2) is a key enzyme of the innate immune system generating superoxide anions (O2•−), precursors of reactive oxygen species. The NOX2 protein complex is composed of six subunits: two membrane proteins (gp91phox and p22phox) forming the catalytic core, three cytosolic proteins (p67phox, p47phox and p40phox) and a small GTPase Rac. The sophisticated activation mechanism of the NADPH oxidase relies on the assembly of cytosolic subunits with the membrane-bound components. A chimeric protein, called ‘Trimera’, composed of the essential domains of the cytosolic proteins p47phox (aa 1-286), p67phox (aa 1-212) and full-length Rac1Q61L, enables a constitutive and robust NOX2 activity in cells without the need of any stimulus. We employed Trimera as a single activating protein of the phagocyte NADPH oxidase in living cells and examined the consequences on the cell physiology of this continuous and long-term NOX activity. We showed that the sustained high level of NOX activity causes acidification of the intracellular pH, triggers apoptosis and leads to local peroxidation of lipids in the membrane. These local damages to the membrane correlate with the strong tendency of the Trimera to clusterize in the plasma membrane observed by FRET-FLIM microscopy.HighlightsTrimera is a tool to trigger a continuous ROS production in living cellsContinuous NOX2 activity causes cytosol acidification and apoptosisROS overproduction leads to localized oxidation of the membrane lipidsTrimera tends to clusterize in the plasma membrane of COSNOX and COS-7 cells

vitreal cells and specialized phagocytes in the chick embryo retina: A TEM and SEM study

1990 ◽  
Vol 48 (3) ◽  
pp. 330-331
Author(s):  
M.A. Cuadros ◽  
M.J. Martinez-Guerrero ◽  
A. Rios
Keyword(s):  
Cell Death ◽  
Plasma Membrane ◽  
Acid Phosphatase ◽  
Chick Embryo ◽  
Basement Membrane ◽  
Sem Images ◽  
Intimate Contact ◽  
Cellular Processes ◽  
Sem Study ◽  
Free Cells

In the chick embryo retina (days 3-4 of incubation), coinciding with an increase in cell death, specialized phagocytes characterized by intense acid phosphatase activity have been described. In these preparations, all free cells in the vitreal humor (vitreal cells) were strongly labeled. Conventional TEM and SEM techniques were used to characterize them and attempt to determine their relationship with retinal phagocytes.Two types of vitreal cells were distinguished. The first are located at some distance from the basement membrane of the neuroepithelium, and are rounded, with numerous vacuoles and thin cytoplasmic prolongations. Images of exo- and or endocytosis were frequent; the cells showed a well-developed Golgi apparatus (Fig. 1) In SEM images, the cells was covered with short cellular processes (Fig. 3). Cells lying parallel to or alongside the basement membrane are elongated. The plasma membrane is frequently in intimate contact with the basement membrane. These cells have generally a large cytoplasmic expansion (Fig. 5).

scholarly journals Regulation of Rho GTPases by RhoGDIs in Human Cancers

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1037 ◽  
Author(s):  
Cho ◽  
Kim ◽  
Baek ◽  
Kim ◽  
Lee
Keyword(s):  
Cell Migration ◽  
Cancer Progression ◽  
Anticancer Agents ◽  
Rho Gtpases ◽  
Rho Gtpase ◽  
Regulatory Mechanisms ◽  
Malignant Phenotype ◽  
Cellular Processes ◽  
Human Cancers

Rho GDP dissociation inhibitors (RhoGDIs) play important roles in various cellular processes, including cell migration, adhesion, and proliferation, by regulating the functions of the Rho GTPase family. Dissociation of Rho GTPases from RhoGDIs is necessary for their spatiotemporal activation and is dynamically regulated by several mechanisms, such as phosphorylation, sumoylation, and protein interaction. The expression of RhoGDIs has changed in many human cancers and become associated with the malignant phenotype, including migration, invasion, metastasis, and resistance to anticancer agents. Here, we review how RhoGDIs control the function of Rho GTPases by regulating their spatiotemporal activity and describe the regulatory mechanisms of the dissociation of Rho GTPases from RhoGDIs. We also discuss the role of RhoGDIs in cancer progression and their potential uses for therapeutic intervention.

scholarly journals Considerations when investigating lncRNA function in vivo

eLife ◽  
2014 ◽  
Vol 3 ◽  
Author(s):  
Andrew R Bassett ◽  
Asifa Akhtar ◽  
Denise P Barlow ◽  
Adrian P Bird ◽  
Neil Brockdorff ◽  
...  
Keyword(s):  
Normal Cell ◽  
Regulatory Elements ◽  
Genomic Locus ◽  
Cellular Processes ◽  
Cell Processes ◽  
Non Coding Rnas ◽  
Per Se ◽  
Dna Regulatory Elements

Although a small number of the vast array of animal long non-coding RNAs (lncRNAs) have known effects on cellular processes examined in vitro, the extent of their contributions to normal cell processes throughout development, differentiation and disease for the most part remains less clear. Phenotypes arising from deletion of an entire genomic locus cannot be unequivocally attributed either to the loss of the lncRNA per se or to the associated loss of other overlapping DNA regulatory elements. The distinction between cis- or trans-effects is also often problematic. We discuss the advantages and challenges associated with the current techniques for studying the in vivo function of lncRNAs in the light of different models of lncRNA molecular mechanism, and reflect on the design of experiments to mutate lncRNA loci. These considerations should assist in the further investigation of these transcriptional products of the genome.

scholarly journals Anthrax toxin rafts into cells

2003 ◽  
Vol 160 (3) ◽  
pp. 295-296 ◽  
Author(s):  
Teymuras Kurzchalia
Keyword(s):  
Plasma Membrane ◽  
Lipid Rafts ◽  
Membrane Receptor ◽  
Anthrax Toxin ◽  
Plasma Membrane Receptor ◽  
Toxin Uptake ◽  
Dependent Pathway

Anthrax toxin binds to a plasma membrane receptor and after endocytosis exerts its deadly effects on the cell. Until now, however, the mechanism of initial toxin uptake was unknown. In this issue, Abrami et al. (2003) demonstrate that toxin oligomerization clusters the anthrax receptor into lipid rafts and this complex is internalized via the clathrin-dependent pathway.

scholarly journals Group I PAKs function downstream of Rac to promote podosome invasion during myoblast fusion in vivo

2012 ◽  
Vol 199 (1) ◽  
pp. 169-185 ◽  
Author(s):  
Rui Duan ◽  
Peng Jin ◽  
Fengbao Luo ◽  
Guofeng Zhang ◽  
Nathan Anderson ◽  
...  
Keyword(s):  
Cell Shape ◽  
Myoblast Fusion ◽  
Small Gtpase ◽  
Fusion Pore ◽  
Cellular Processes ◽  
Filament Assembly ◽  
Group I ◽  
Redundant Functions ◽  
Shape Changes

The p21-activated kinases (PAKs) play essential roles in diverse cellular processes and are required for cell proliferation, apoptosis, polarity establishment, migration, and cell shape changes. Here, we have identified a novel function for the group I PAKs in cell–cell fusion. We show that the two Drosophila group I PAKs, DPak3 and DPak1, have partially redundant functions in myoblast fusion in vivo, with DPak3 playing a major role. DPak3 is enriched at the site of fusion colocalizing with the F-actin focus within a podosome-like structure (PLS), and promotes actin filament assembly during PLS invasion. Although the small GTPase Rac is involved in DPak3 activation and recruitment to the PLS, the kinase activity of DPak3 is required for effective PLS invasion. We propose a model whereby group I PAKs act downstream of Rac to organize the actin filaments within the PLS into a dense focus, which in turn promotes PLS invasion and fusion pore initiation during myoblast fusion.

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