scholarly journals Tribbles in normal and malignant haematopoiesis

2015 ◽  
Vol 43 (5) ◽  
pp. 1112-1115 ◽  
Author(s):  
Sarah J. Stein ◽  
Ethan A. Mack ◽  
Kelly S. Rome ◽  
Warren S. Pear
Keyword(s):  
E3 Ligase ◽  
Cell Types ◽  
Protein Family ◽  
Conserved Motifs ◽  
Tissue Specific ◽  
Cellular Events ◽  
Haematopoietic Cells ◽  
Evolutionarily Conserved ◽  
Multiple Cell

The tribbles protein family, an evolutionarily conserved group of pseudokinases, have been shown to regulate multiple cellular events including those involved in normal and malignant haematopoiesis. The three mammalian Tribbles homologues, Trib1, Trib2 and Trib3 are characterized by conserved motifs, including a pseudokinase domain and a C-terminal E3 ligase-binding domain. In this review, we focus on the role of Trib (mammalian Tribbles homologues) proteins in mammalian haematopoiesis and leukaemia. The Trib proteins show divergent expression in haematopoietic cells, probably indicating cell-specific functions. The roles of the Trib proteins in oncogenesis are also varied and appear to be tissue-specific. Finally, we discuss the potential mechanisms by which the Trib proteins preferentially regulate these processes in multiple cell types.

scholarly journals Prohibitin: A hypothetical target for sex-based new therapeutics for metabolic and immune diseases

2019 ◽  
Vol 244 (2) ◽  
pp. 157-170 ◽  
Author(s):  
Suresh Mishra ◽  
BL Grégoire Nyomba
Keyword(s):  
Sex Differences ◽  
Sex Steroids ◽  
Immune Cell ◽  
Cell Types ◽  
Immune Functions ◽  
Evolutionarily Conserved ◽  
Health And Disease ◽  
Multiple Cell ◽  
Membrane Signaling

Adipose and immune functions display sex differences and are influenced by sex steroid hormones in health and disease. However, effector molecules that mediate the effects of sex steroids and determine sex differences in adipocytes and immune cells are largely unknown. Sex differences are known to exist in mitochondrial biology, and mitochondria play a crucial role in adipocyte and immune cell functions. In fact, mitochondrial dysregulation is a common finding in a number of diseases that exhibit sex differences. It is, therefore, possible that mitochondria carry out sex-dimorphic functions. Prohibitin, an evolutionarily conserved pleiotropic protein, known to function as a mitochondrial chaperone, has multifaceted relationship with sex steroids and their receptors. New evidence indicates that prohibitin has roles in sex differences in multiple cell and tissue types, including adipocytes, macrophages, and dendritic cells. Transgenic mice overexpressing prohibitin in adipocytes, macrophages, and dendritic cells exhibit sex differences in metabolic and immune phenotypes, mediated through mitochondrial and plasma membrane signaling functions of prohibitin. Thus, the discovery of prohibitin as mediating the effects of sex steroids in multiple cell types has opened a new research direction to study the relationship between sex steroids and mitochondrial proteins and their impact on sex differences in health and disease. In this opinion article, we will provide a personal perspective of the role of prohibitin with cellular compartment- and tissue-specific functions in mediating sex-dimorphic adipose and immune functions. We believe that prohibitin is a potential target for sex-based new therapeutics for metabolic and immune diseases. Impact statement Traditional sex-related biases in research are now obsolete, and it is important to identify the sex of humans, animals, and even cells in research protocols, due to the role of sex as a fundamental facet of biology, predisposition to disease, and response to therapy. Genetic sex, epigenetics and hormonal regulations, generate sex-dimorphisms. Recent investigations acknowledge sex differences in metabolic and immune health as well as chronic diseases. Prohibitin, an evolutionarily conserved molecule, has pleotropic functions in mitochondrial housekeeping, plasma membrane signaling, and nuclear genetic transcription. Studies in adipocytes, macrophages, and transgenic mice indicate that prohibitin interacts with sex steroids and plays a role in mediating sex differences in adipose tissues and immune cell types. Prohibitin may, depending on context, modulate predisposition to chronic metabolic diseases and malignancy and, because of these attributes, could be a target for sex-based therapies of metabolic and immune-related diseases as well as cancer.

scholarly journals Microtubule–microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes

2016 ◽  
Vol 113 (34) ◽  
pp. E4995-E5004 ◽  
Author(s):  
Wen Lu ◽  
Michael Winding ◽  
Margot Lakonishok ◽  
Jill Wildonger ◽  
Vladimir I. Gelfand
Keyword(s):  
Cytoplasmic Streaming ◽  
Cell Types ◽  
Nurse Cells ◽  
Wild Type ◽  
Actin Cortex ◽  
Microtubule Motor ◽  
Multiple Cell ◽  
Cytoplasmic Microtubules ◽  
Two Populations

Cytoplasmic streaming in Drosophila oocytes is a microtubule-based bulk cytoplasmic movement. Streaming efficiently circulates and localizes mRNAs and proteins deposited by the nurse cells across the oocyte. This movement is driven by kinesin-1, a major microtubule motor. Recently, we have shown that kinesin-1 heavy chain (KHC) can transport one microtubule on another microtubule, thus driving microtubule–microtubule sliding in multiple cell types. To study the role of microtubule sliding in oocyte cytoplasmic streaming, we used a Khc mutant that is deficient in microtubule sliding but able to transport a majority of cargoes. We demonstrated that streaming is reduced by genomic replacement of wild-type Khc with this sliding-deficient mutant. Streaming can be fully rescued by wild-type KHC and partially rescued by a chimeric motor that cannot move organelles but is active in microtubule sliding. Consistent with these data, we identified two populations of microtubules in fast-streaming oocytes: a network of stable microtubules anchored to the actin cortex and free cytoplasmic microtubules that moved in the ooplasm. We further demonstrated that the reduced streaming in sliding-deficient oocytes resulted in posterior determination defects. Together, we propose that kinesin-1 slides free cytoplasmic microtubules against cortically immobilized microtubules, generating forces that contribute to cytoplasmic streaming and are essential for the refinement of posterior determinants.

Spalt modifies EGFR-mediated induction of chordotonal precursors in the embryonic PNS of Drosophila promoting the development of oenocytes

Development ◽  
2001 ◽  
Vol 128 (5) ◽  
pp. 711-722 ◽  
Author(s):  
T.E. Rusten ◽  
R. Cantera ◽  
J. Urban ◽  
G. Technau ◽  
F.C. Kafatos ◽  
...  
Keyword(s):  
Nervous System ◽  
Cell Fate ◽  
System Development ◽  
Cell Types ◽  
Nervous System Development ◽  
Dual Function ◽  
Evolutionarily Conserved ◽  
A Cell ◽  
And Migration

Genes of the spalt family encode nuclear zinc finger proteins. In Drosophila melanogaster, they are necessary for the establishment of head/trunk identity, correct tracheal migration and patterning of the wing imaginal disc. Spalt proteins display a predominant pattern of expression in the nervous system, not only in Drosophila but also in species of fish, mouse, frog and human, suggesting an evolutionarily conserved role for these proteins in nervous system development. Here we show that Spalt works as a cell fate switch between two EGFR-induced cell types, the oenocytes and the precursors of the pentascolopodial organ in the embryonic peripheral nervous system. We show that removal of spalt increases the number of scolopodia, as a result of extra secondary recruitment of precursor cells at the expense of the oenocytes. In addition, the absence of spalt causes defects in the normal migration of the pentascolopodial organ. The dual function of spalt in the development of this organ, recruitment of precursors and migration, is reminiscent of its role in tracheal formation and of the role of a spalt homologue, sem-4, in the Caenorhabditis elegans nervous system.

scholarly journals Generation of a Quantitative Luciferase Reporter for Sox9 SUMOylation

2020 ◽  
Vol 21 (4) ◽  
pp. 1274
Author(s):  
Hideka Saotome ◽  
Atsumi Ito ◽  
Atsushi Kubo ◽  
Masafumi Inui
Keyword(s):  
Cell Types ◽  
Live Cells ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Post Translational Modifications ◽  
Extracellular Signal ◽  
Multiple Cell ◽  
Sox9 Activity ◽  
Reporter Signal

Sox9 is a master transcription factor for chondrogenesis, which is essential for chondrocyte proliferation, differentiation, and maintenance. Sox9 activity is regulated by multiple layers, including post-translational modifications, such as SUMOylation. A detection method for visualizing the SUMOylation in live cells is required to fully understand the role of Sox9 SUMOylation. In this study, we generated a quantitative reporter for Sox9 SUMOylation that is based on the NanoBiT system. The simultaneous expression of Sox9 and SUMO1 constructs that are conjugated with NanoBiT fragments in HEK293T cells induced luciferase activity in SUMOylation target residue of Sox9-dependent manner. Furthermore, the reporter signal could be detected from both cell lysates and live cells. The signal level of our reporter responded to the co-expression of SUMOylation or deSUMOylation enzymes by several fold, showing dynamic potency of the reporter. The reporter was active in multiple cell types, including ATDC5 cells, which have chondrogenic potential. Finally, using this reporter, we revealed a extracellular signal conditions that can increase the amount of SUMOylated Sox9. In summary, we generated a novel reporter that was capable of quantitatively visualizing the Sox9-SUMOylation level in live cells. This reporter will be useful for understanding the dynamism of Sox9 regulation during chondrogenesis.

scholarly journals Nitric Oxide Transiently Converts Synaptic Inhibition to Excitation in Retinal Amacrine Cells

2006 ◽  
Vol 95 (5) ◽  
pp. 2866-2877 ◽  
Author(s):  
Brian Hoffpauir ◽  
Emily McMains ◽  
Evanna Gleason
Keyword(s):  
Nitric Oxide ◽  
Hippocampal Neurons ◽  
Reversal Potential ◽  
Amacrine Cells ◽  
Cell Types ◽  
Synaptic Function ◽  
Positive Shift ◽  
Gabaergic Synapses ◽  
Multiple Cell

Nitric oxide (NO) is generated by multiple cell types in the vertebrate retina, including amacrine cells. We investigate the role of NO in the modulation of synaptic function using a culture system containing identified retinal amacrine cells. We find that moderate concentrations of NO alter GABAA receptor function to produce an enhancement of the GABA-gated current. Higher concentrations of NO also enhance GABA-gated currents, but this enhancement is primarily due to a substantial positive shift in the reversal potential of the current. Several pieces of evidence, including a similar effect on glycine-gated currents, indicate that the positive shift is due to an increase in cytosolic Cl−. This change in the chloride distribution is especially significant because it can invert the sign of GABA- and glycine-gated voltage responses. Furthermore, current- and voltage-clamp recordings from synaptic pairs of GABAergic amacrine cells demonstrate that NO transiently converts signaling at GABAergic synapses from inhibition to excitation. Persistence of the NO-induced shift in ECl− in the absence of extracellular Cl− indicates that the increase in cytosolic Cl− is due to release of Cl− from an internal store. An NO-dependent release of Cl− from an internal store is also demonstrated for rat hippocampal neurons indicating that this mechanism is not restricted to the avian retina. Thus signaling in the CNS can be fundamentally altered by an NO-dependent mobilization of an internal Cl− store.

scholarly journals Nckβ Adapter Controls Neuritogenesis by Maintaining the Cellular Paxillin Level

2007 ◽  
Vol 27 (17) ◽  
pp. 6001-6011 ◽  
Author(s):  
Shengxi Guan ◽  
Mei Chen ◽  
David Woodley ◽  
Wei Li
Keyword(s):  
Pc12 Cells ◽  
Cortical Neurons ◽  
State Level ◽  
Cell Types ◽  
Steady State Level ◽  
Down Regulation ◽  
Evolutionarily Conserved ◽  
Rat Cortical Neurons ◽  
Interfering Rna

ABSTRACT The SH2/SH3 adapter Nck has an evolutionarily conserved role in neurons, linking the cell surface signals to actin cytoskeleton-mediated responses. The mechanism, however, remains poorly understood. We have investigated the role of Nck/Nckα/Nck1 versus Grb4/Nckβ/Nck2 side-by-side in the process of mammalian neuritogenesis. Here we show that permanent genetic silencing of Nckβ, but not Nckα, completely blocked nerve growth factor-induced neurite outgrowth in PC12 cells and dramatically disrupted the axon and dendrite tree in primary rat cortical neurons. By screening for changes among the components reportedly present in complex with Nck, we found that the steady-state level of paxillin was significantly reduced in Nckβ knockdown, but not Nckα knockdown, neurons. Interestingly, Nckβ knockdown did not affect the paxillin level in glial cells and several other cell types of various tissue origins. Genetic silencing of paxillin blocked neuritogenesis, just like Nckβ knockdown. Reintroducing a nondegradable Nckβ into Nckβ short interfering RNA-expressing PC12 cells rescued paxillin from down-regulation and allowed the resumption of neuritogenesis. Forced expression of paxillin in Nckβ knockdown PC12 also rescued its capacity for neuritogenesis. Finally, Nckβ, but not Nckα, binds strongly to paxillin and treatment of the neurons with proteosome inhibitors prevented paxillin down-regulation in Nckβ knockdown neurons. Thus, Nckβ maintains paxillin stability during neuritogenesis.

scholarly journals Wound Healing and Omega-6 Fatty Acids: From Inflammation to Repair

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Jéssica R. Silva ◽  
Beatriz Burger ◽  
Carolina M. C. Kühl ◽  
Thamiris Candreva ◽  
Mariah B. P. dos Anjos ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Wound Healing ◽  
Current Knowledge ◽  
Phagocytic Capacity ◽  
Cellular Events ◽  
Species Survival ◽  
Evolutionarily Conserved ◽  
Omega 6 ◽  
Cell Migration And Proliferation

Wound healing is an evolutionarily conserved process that is essential for species survival. Wound healing involves a series of biochemical and cellular events that are tightly controlled, divided into 3 concomitant and overlapping phases: inflammation, proliferation, and remodelling. Poor wound healing or a chronic wound represents a silent epidemic that affects billions of people worldwide. Considering the involvement of immune cells in its resolution, recent studies are focused on investigating the roles of immune nutrients such as amino acids, minerals, and fatty acids on wound healing. Among the fatty acids, much attention has been given to omega-6 (ω-6) fatty acids since they can modulate cell migration and proliferation, phagocytic capacity, and production of inflammatory mediators. The present review summarizes current knowledge about the role of ω-6 fatty acids in the wound healing context.

scholarly journals The Evolutionary Conserved Transmembrane BAX Inhibitor Motif (TMBIM) Containing Protein Family is Essential for the Development and Survival of Drosophila Melanogaster

2020 ◽  
Author(s):  
Li Zhang ◽  
Sebastian Buhr ◽  
Vibha Prasad ◽  
Aaron Voigt ◽  
Axel Methner
Keyword(s):  
Drosophila Melanogaster ◽  
Genetic Interaction ◽  
Family Members ◽  
Protein Family ◽  
Tissue Specific ◽  
Similar Expression Pattern ◽  
Evolutionarily Conserved ◽  
Extended Lifespan ◽  
Ph Dependent ◽  
Er Calcium

Abstract The Transmembrane BAX Inhibitor Motif (TMBIM) protein family consists of six evolutionarily conserved hydrophobic proteins that affect programmed cell death and the regulation of intracellular calcium levels. The bacterial orthologue BsYetJ is a pH-dependent calcium channel. We here identified six TMBIM family members in Drosophila melanogaster and studied the effect of their RNAi-mediated knockdown using ubiquitous and tissue-specific drivers. Mammalian TMBIM6 and TMBIM5 have obvious orthologs while this is more dubious for the other family members. Ubiquitous knockdown of family members dmTMBIM1,4,5, and 6 caused failed eclosing and tissue-specific knockdown resulted in a dramatically decreased lifespan. On the contrary, knockdown of dmTMBIM3, surprisingly, extended lifespan. Only knockdown of dmTMBIM6 increased the ER calcium levels of Pdf neurons. Neural knockdown of dmTMBIM2,3, and 4 increased ER stress, as indicated by increased Xbp1 splicing. Interestingly, TMBIM1 and TMBIM6 have a very similar expression pattern and their knockdown phenocopied each other. Also, knockdown of TMBIM1 resulted in upregulation of TMBIM6 and vice versa further suggesting a genetic interaction between these two genes. Our data demonstrate that most TMBIM proteins are essential for fly development and survival but, despite their shared protein structure, affect cell survival through different mechanisms.

Role of presympathetic C1 neurons in the sympatholytic and hypotensive effects of clonidine in rats

2000 ◽  
Vol 279 (5) ◽  
pp. R1753-R1762 ◽  
Author(s):  
Ann M. Schreihofer ◽  
Patrice G. Guyenet
Keyword(s):  
Extracellular Recording ◽  
Splanchnic Nerve ◽  
Cell Types ◽  
Ventrolateral Medulla ◽  
Thoracic Spinal Cord ◽  
Catecholaminergic Neurons ◽  
Thoracic Spinal ◽  
Multiple Cell ◽  
Rvlm Neuron

The rostral ventrolateral medulla (RVLM) may play an important role in the sympatholytic and hypotensive effects of clonidine. The present study examined which type of presympathetic RVLM neuron is inhibited by clonidine, and whether the adrenergic presympathetic RVLM neurons are essential for clonidine-induced sympathoinhibition. In chloralose-anesthetized and ventilated rats, clonidine (10 μg/kg iv) decreased arterial pressure (116 ± 6 to 84 ± 2 mmHg) and splanchnic nerve activity (93 ± 3% from baseline). Extracellular recording and juxtacellular labeling of barosensitive bulbospinal RVLM neurons revealed that most cells were inhibited by clonidine (26/28) regardless of phenotype [tyrosine hydroxylase (TH)-immunoreactive cells: 48 ± 7%; non-TH-immunoreactive cells: 42 ± 5%], although the inhibition of most neurons was modest compared with the observed sympathoinhibition. Depletion of most bulbospinal catecholaminergic neurons, including 76 ± 5% of the rostral C1 cells, by microinjection of saporin anti-dopamine β-hydroxylase into the thoracic spinal cord (levels T2 and T4, 42 ng · 200 nl−1 · side−1) did not alter the sympatholytic or hypotensive effects of clonidine. These data show that although clonidine inhibits presympathetic C1 neurons, bulbospinal catecholaminergic neurons do not appear to be essential for the sympatholytic and hypotensive effects of systemically administered clonidine. Instead, the sympatholytic effect of clonidine is likely the result of a combination of effects on multiple cell types both within and outside the RVLM.

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