scholarly journals Extrinsic Factors Regulating Dendritic Patterning

2021 ◽  
Vol 14 ◽  
Author(s):  
Tzu-Yang Lin ◽  
Pei-Ju Chen ◽  
Hung-Hsiang Yu ◽  
Chao-Ping Hsu ◽  
Chi-Hon Lee
Keyword(s):  
Dendritic Growth ◽  
Developmental Stages ◽  
Lipid Synthesis ◽  
Supporting Cells ◽  
Extrinsic Factors ◽  
Dendritic Trees ◽  
Downstream Signaling ◽  
Neuronal Identity ◽  
Receptor Interactions ◽  
Dendrite Morphogenesis

Stereotypic dendrite arborizations are key morphological features of neuronal identity, as the size, shape and location of dendritic trees determine the synaptic input fields and how information is integrated within developed neural circuits. In this review, we focus on the actions of extrinsic intercellular communication factors and their effects on intrinsic developmental processes that lead to dendrite patterning. Surrounding neurons or supporting cells express adhesion receptors and secreted proteins that respectively, act via direct contact or over short distances to shape, size, and localize dendrites during specific developmental stages. The different ligand-receptor interactions and downstream signaling events appear to direct dendrite morphogenesis by converging on two categorical mechanisms: local cytoskeletal and adhesion modulation and global transcriptional regulation of key dendritic growth components, such as lipid synthesis enzymes. Recent work has begun to uncover how the coordinated signaling of multiple extrinsic factors promotes complexity in dendritic trees and ensures robust dendritic patterning.

scholarly journals Lipid Dynamics, Identification, and Expression Patterns of Fatty Acid Synthase Genes in an Endoparasitoid, Meteorus pulchricornis (Hymenoptera: Braconidae)

2020 ◽  
Vol 21 (17) ◽  
pp. 6228
Author(s):  
Jiao Wang ◽  
Li-Wei Shen ◽  
Xiao-Rong Xing ◽  
Yu-Qi Xie ◽  
Yi-Jiangcheng Li ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Content ◽  
Fatty Acid Synthase ◽  
Developmental Stages ◽  
Adult Stage ◽  
Expression Patterns ◽  
Lipid Synthesis ◽  
Open Reading Frames ◽  
Lipid Dynamics ◽  
Meteorus Pulchricornis

In insect parasitoids, fatty acid synthases (FASs) have received less attention and their roles associated with lipogenesis loss are far from clear. Meteorus pulchricornis is a solitary endoparasitoid wasp of many larvae of lepidopteran pests. The lipid content during developmental stages of M. pulchricornis was measured; it was higher in the larval and pupal stages but declined from six-day-old pupae. Lipid accumulation constantly decreased in the adult stage, even after feeding on honey solutions. To investigate the roles of FASs in lipid synthesis in M. pulchricornis, four FAS genes (MpulFAS1~4) were identified from the transcriptome database of M. pulchricornis. All FAS genes included full-length open reading frames and shared 72–79% similarity with the sequences of Microplitis demolitor. qRT-PCR validation showed that all four FASs had the highest expression after the adult wasps were fed on honey diets. MpulFAS1 and MpulFAS2 reached their expression peaks at the adult stage but MpulFAS3 and MpulFAS4 peaked at the larval stage. To further study the function of FASs, dsRNA injection knocked down the expression of four MpulFASs and resulted in a significant decline of lipid content at the adult stage in M. pulchricornis. Results from this study suggest that M. pulchricornis adults cannot accumulate lipid content effectively and FASs may still contribute to lipid synthesis in the adult stage. This broadens the knowledge on the ability of lipid synthesis in parasitoid wasps and provides insight into the roles of FASs in insects with parasitic life-history traits.

scholarly journals Calcium in the Backstage of Malaria Parasite Biology

2021 ◽  
Vol 11 ◽  
Author(s):  
Lucas Silva de Oliveira ◽  
Marcos Rodrigo Alborghetti ◽  
Renata Garcia Carneiro ◽  
Izabela Marques Dourado Bastos ◽  
Rogerio Amino ◽  
...  
Keyword(s):  
Life Cycle ◽  
Protein Kinases ◽  
Malaria Parasite ◽  
Developmental Stages ◽  
Receptor Gene ◽  
Food Vacuole ◽  
Parasite Development ◽  
Cell Infection ◽  
Parasite Life Cycle ◽  
Downstream Signaling

The calcium ion (Ca2+) is a ubiquitous second messenger involved in key biological processes in prokaryotes and eukaryotes. In Plasmodium species, Ca2+ signaling plays a central role in the parasite life cycle. It has been associated with parasite development, fertilization, locomotion, and host cell infection. Despite the lack of a canonical inositol-1,4,5-triphosphate receptor gene in the Plasmodium genome, pharmacological evidence indicates that inositol-1,4,5-triphosphate triggers Ca2+ mobilization from the endoplasmic reticulum. Other structures such as acidocalcisomes, food vacuole and mitochondria are proposed to act as supplementary intracellular Ca2+ reservoirs. Several Ca2+-binding proteins (CaBPs) trigger downstream signaling. Other proteins with no EF-hand motifs, but apparently involved with CaBPs, are depicted as playing an important role in the erythrocyte invasion and egress. It is also proposed that a cross-talk among kinases, which are not members of the family of Ca2+-dependent protein kinases, such as protein kinases G, A and B, play additional roles mediated indirectly by Ca2+ regulation. This statement may be extended for proteins directly related to invasion or egress, such as SUB1, ERC, IMC1I, IMC1g, GAP45 and EBA175. In this review, we update our understanding of aspects of Ca2+-mediated signaling correlated to the developmental stages of the malaria parasite life cycle.

scholarly journals Emerging Roles of Filopodia and Dendritic Spines in Motoneuron Plasticity during Development and Disease

2016 ◽  
Vol 2016 ◽  
pp. 1-31 ◽  
Author(s):  
Refik Kanjhan ◽  
Peter G. Noakes ◽  
Mark C. Bellingham
Keyword(s):  
Dendritic Growth ◽  
Gene Knockout ◽  
Spine Density ◽  
Motor Tasks ◽  
Dendritic Trees ◽  
Sodium Calcium ◽  
Complex Motor ◽  
Distribution Shifts ◽  
Circuit Formation ◽  
Energy Dependent

Motoneurons develop extensive dendritic trees for receiving excitatory and inhibitory synaptic inputs to perform a variety of complex motor tasks. At birth, the somatodendritic domains of mouse hypoglossal and lumbar motoneurons have dense filopodia and spines. Consistent with Vaughn’s synaptotropic hypothesis, we propose a developmental unified-hybrid model implicating filopodia in motoneuron spinogenesis/synaptogenesis and dendritic growth and branching critical for circuit formation and synaptic plasticity at embryonic/prenatal/neonatal period. Filopodia density decreases and spine density initially increases until postnatal day 15 (P15) and then decreases by P30. Spine distribution shifts towards the distal dendrites, and spines become shorter (stubby), coinciding with decreases in frequency and increases in amplitude of excitatory postsynaptic currents with maturation. In transgenic mice, either overexpressing the mutated human Cu/Zn-superoxide dismutase (hSOD1G93A) gene or deficient in GABAergic/glycinergic synaptic transmission (gephyrin, GAD-67, or VGAT gene knockout), hypoglossal motoneurons develop excitatory glutamatergic synaptic hyperactivity. Functional synaptic hyperactivity is associated with increased dendritic growth, branching, and increased spine and filopodia density, involving actin-based cytoskeletal and structural remodelling. Energy-dependent ionic pumps that maintain intracellular sodium/calcium homeostasis are chronically challenged by activity and selectively overwhelmed by hyperactivity which eventually causes sustained membrane depolarization leading to excitotoxicity, activating microglia to phagocytose degenerating neurons under neuropathological conditions.

scholarly journals Transcription Factors Associated With IL-15 Cytokine Signaling During NK Cell Development

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiang Wang ◽  
Xiang-Yu Zhao
Keyword(s):  
Nk Cells ◽  
Developmental Stages ◽  
Nk Cell ◽  
Current Knowledge ◽  
Cell Development ◽  
Cytokine Signaling ◽  
Hematopoietic Stem ◽  
Downstream Signaling ◽  
Downstream Target

Natural killer (NK) cells are lymphocytes primarily involved in innate immunity and possess important functional properties in anti-viral and anti-tumor responses; thus, these cells have broad potential for clinical utilization. NK cells originate from hematopoietic stem cells (HSCs) through the following two independent and continuous processes: early commitment from HSCs to IL-15-responsive NK cell progenitors (NKPs) and subsequent differentiation into mature NK cells in response to IL-15. IL-15 is the most important cytokine for NK cell development, is produced by both hematopoietic and nonhematopoietic cells, and functions through a distinct delivery process termed transpresentation. Upon being transpresented to NK cells, IL-15 contributes to NK cell development via the activation of several downstream signaling pathways, including the Ras–MEK–MAPK, JAK–STAT5, and PI3K–ATK–mTOR pathways. Nonetheless, the exact role of IL-15 in NK cell development has not been discussed in a consecutive and comprehensive manner. Here, we review current knowledge about the indispensable role of IL-15 in NK cell development and address which cells produce IL-15 to support NK cell development and when IL-15 exerts its function during multiple developmental stages. Specifically, we highlight how IL-15 supports NK cell development by elucidating the distinct transpresentation of IL-15 to NK cells and revealing the downstream target of IL-15 signaling during NK cell development.

scholarly journals The ShcD phosphotyrosine adaptor protein exhibits novel binding characteristics with the TrkA neurotrophin receptor

SURG Journal ◽  
1969 ◽  
Vol 2 (1) ◽  
pp. 59-70
Author(s):  
Melanie Wills ◽  
Nina Jones
Keyword(s):  
Adaptor Protein ◽  
Neurotrophin Receptor ◽  
Binding Characteristics ◽  
Tyrosine Residues ◽  
Sh2 Domains ◽  
Downstream Signaling ◽  
Cytoplasmic Tails ◽  
Receptor Interactions ◽  
Src Homology ◽  
The Brain

Newly revealed ShcD has been characterized as an intracellular phosphotyrosine adaptor protein belonging to the Src homology and collagen (Shc) family. These scaffolding molecules facilitate receptor-mediated signal transduction through their ability to selectively recognize and bind, via PTB and SH2 domains, to phosphorylated tyrosine residues in the cytoplasmic tails of a variety of activated receptors. A central CH1 domain couples to downstream signaling molecules including Grb2. ShcD is most similar in form to ShcA; however, unlike the latter, its expression in the mouse is localized to the brain and skeletal muscle. Consistent with this observation, we report that human ShcD is able to bind the TrkA neurotrophin receptor responsive to nerve growth factor (NGF). This interaction is similar to that of other Shc proteins in that it is strongly influenced by the TrkA Tyr 490 residue, and results in ShcD phosphorylation. Surprisingly, we find that both the PTB and SH2 domains of ShcD impact its ability to complex with TrkA, in contrast to the PTB-mediated interaction documented for traditional Shc proteins. TrkA binding analyses performed with different ShcD mutants suggest that the contributions of the PTB and SH2 domains supercede simple co operativity, and are in fact reminiscent of auto-regulatory mechanisms. Here we report both the canonical and atypical characteristics of the ShcD / TrkA interaction, including novel proposed models of adaptor-receptor interactions.

scholarly journals From Endoderm to Progenitors: An Update on the Early Steps of Thyroid Morphogenesis in the Zebrafish

2021 ◽  
Vol 12 ◽  
Author(s):  
Federica Marelli ◽  
Giuditta Rurale ◽  
Luca Persani
Keyword(s):  
Developmental Stages ◽  
Developmental Process ◽  
Experimental Models ◽  
Extrinsic Factors ◽  
Comprehensive Picture ◽  
Central Interest ◽  
Endodermal Cells ◽  
Gland Development ◽  
Early Developmental ◽  
Developmental Windows

The mechanisms underlying thyroid gland development have a central interest in biology and this review is aimed to provide an update on the recent advancements on the early steps of thyroid differentiation that were obtained in the zebrafish, because this teleost fish revealed to be a suitable organism to study the early developmental stages. Physiologically, the thyroid precursors fate is delineated by the appearance among the endoderm cells of the foregut of a restricted cell population expressing specific transcription factors, including pax2a, nkx2.4b, and hhex. The committed thyroid primordium first appears as a thickening of the pharyngeal floor of the anterior endoderm, that subsequently detaches from the floor and migrates to its final location where it gives rise to the thyroid hormone-producing follicles. At variance with mammalian models, thyroid precursor differentiation in zebrafish occurs early during the developmental process before the dislocation to the eutopic positioning of thyroid follicles. Several pathways have been implicated in these early events and nowadays there is evidence of a complex crosstalk between intrinsic (coming from the endoderm and thyroid precursors) and extrinsic factors (coming from surrounding tissues, as the cardiac mesoderm) whose organization in time and space is probably required for the proper thyroid development. In particular, Notch, Shh, Fgf, Bmp, and Wnt signaling seems to be required for the commitment of endodermal cells to a thyroid fate at specific developmental windows of zebrafish embryo. Here, we summarize the recent findings produced in the various zebrafish experimental models with the aim to define a comprehensive picture of such complicated puzzle.

scholarly journals Genetic analyses in mouse fibroblast and melanoma cells demonstrate novel roles for PDGF-AB ligand and PDGF receptor alpha

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Julie L. Kadrmas ◽  
Mary C. Beckerle ◽  
Masaaki Yoshigi
Keyword(s):  
Gene Editing ◽  
Cultured Cells ◽  
Growth Factor Receptor ◽  
Mouse Fibroblast ◽  
Complete Understanding ◽  
Future Studies ◽  
Downstream Signaling ◽  
Receptor Interactions ◽  
Rapid Formation ◽  
Pdgfr Beta

Abstract Platelet Derived Growth Factor Receptor (PDGFR) signaling is a central mitogenic pathway in development, as well as tissue repair and homeostasis. The rules governing the binding of PDGF ligand to the receptor to produce activation and downstream signaling have been well defined over the last several decades. In cultured cells after a period of serum deprivation, treatment with PDGF leads to the rapid formation of dramatic, actin-rich Circular Dorsal Ruffles (CDRs). Using CDRs as a robust visual readout of early PDGFR signaling, we have identified several contradictory elements in the widely accepted model of PDGF activity. Employing CRISPR/Cas9 gene editing to disrupt the Pdgfra gene in two different murine cell lines, we show that in addition to the widely accepted function for PDGFR-beta in CDR formation, PDGFR-alpha is also clearly capable of eliciting CDRs. Moreover, we demonstrate activity for heterodimeric PDGF-AB ligand in the vigorous activation of PDGFR-beta homodimers to produce CDRs. These findings are key to a more complete understanding of PDGF ligand-receptor interactions and their downstream signaling consequences. This knowledge will allow for more rigorous experimental design in future studies of PDGFR signaling and its contributions to development and disease.

scholarly journals Fringe Glycosyltransferases Differentially Modulate Notch1 Proteolysis Induced by Delta1 and Jagged1

2005 ◽  
Vol 16 (2) ◽  
pp. 927-942 ◽  
Author(s):  
Liang-Tung Yang ◽  
James T. Nichols ◽  
Christine Yao ◽  
Jennifer O. Manilay ◽  
Ellen A. Robey ◽  
...  
Keyword(s):  
Notch Signaling ◽  
3T3 Cells ◽  
Binding Studies ◽  
Differential Effects ◽  
Downstream Signaling ◽  
Notch1 Signaling ◽  
Data Support ◽  
Receptor Interactions ◽  
Fringe Proteins ◽  
Nih 3T3

Fringe O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch signaling by potentiating signaling induced by Delta-like ligands, while inhibiting signaling induced by Serrate/Jagged1 ligands. Based on binding studies, the differential effects of Drosophila fringe (DFng) on Notch signaling are thought to result from alterations in Notch glycosylation that enhance binding of Delta to Notch but reduce Serrate binding. Here, we report that expression of mammalian fringe proteins (Lunatic [LFng], Manic [MFng], or Radical [RFng] Fringe) increased Delta1 binding and activation of Notch1 signaling in 293T and NIH 3T3 cells. Although Jagged1-induced signaling was suppressed by LFng and MFng, RFng enhanced signaling induced by either Delta1 or Jagged1, underscoring the diversity of mammalian fringe glycosyltransferases in regulating signaling downstream of different ligand-receptor combinations. Interestingly, suppression of Jagged1-induced Notch1 signaling did not correlate with changes in Jagged1 binding as found for Delta1. Our data support the idea that fringe glycosylation increases Delta1 binding to potentiate signaling, but we propose that although fringe glycosylation does not reduce Jagged1 binding to Notch1, the resultant ligand–receptor interactions do not effectively promote Notch1 proteolysis required for activation of downstream signaling events.

scholarly journals The Roles of Post-Translational Modifications on mTOR Signaling

2021 ◽  
Vol 22 (4) ◽  
pp. 1784
Author(s):  
Shasha Yin ◽  
Liu Liu ◽  
Wenjian Gan
Keyword(s):  
Metabolic Diseases ◽  
Lipid Synthesis ◽  
Genetic Alterations ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Human Diseases ◽  
Post Translational Modifications ◽  
Downstream Signaling ◽  
Cellular Processes ◽  
Almost All

The mechanistic target of rapamycin (mTOR) is a master regulator of cell growth, proliferation, and metabolism by integrating various environmental inputs including growth factors, nutrients, and energy, among others. mTOR signaling has been demonstrated to control almost all fundamental cellular processes, such as nucleotide, protein and lipid synthesis, autophagy, and apoptosis. Over the past fifteen years, mapping the network of the mTOR pathway has dramatically advanced our understanding of its upstream and downstream signaling. Dysregulation of the mTOR pathway is frequently associated with a variety of human diseases, such as cancers, metabolic diseases, and cardiovascular and neurodegenerative disorders. Besides genetic alterations, aberrancies in post-translational modifications (PTMs) of the mTOR components are the major causes of the aberrant mTOR signaling in a number of pathologies. In this review, we summarize current understanding of PTMs-mediated regulation of mTOR signaling, and also update the progress on targeting the mTOR pathway and PTM-related enzymes for treatment of human diseases.

scholarly journals Neurotrophic control of size regulation during axolotl limb regeneration

2021 ◽  
Author(s):  
Kaylee M. Wells-Enright ◽  
Kristina Kelley ◽  
Mary Baumel ◽  
Warren A. Vieira ◽  
Catherine D. McCusker
Keyword(s):  
Rapid Growth ◽  
Developmental Stages ◽  
Limb Regeneration ◽  
Neurotrophic Control ◽  
Final Size ◽  
Extrinsic Factors ◽  
Mexican Axolotl ◽  
Host Environment ◽  
Size Regulation

AbstractThe mechanisms that regulate the sizing of the regenerating limb in tetrapods such as the Mexican axolotl are unknown. Upon the completion of the developmental stages of regeneration, when the regenerative organ known as the blastema completes patterning and differentiation, the limb regenerate is proportionally small in size. It then undergoes a phase of regeneration that we have called the “tiny-limb” stage, that is defined by rapid growth until the regenerate reaches the proportionally appropriate size. In the current study we have characterized this growth and have found that signaling from the limb nerves is required for its maintenance. Using the regenerative assay known as the Accessory Limb Model, we have found that the size of the limb can be positively and negatively manipulated by nerve abundance. We have additionally developed a new regenerative assay called the Neural Modified-ALM (NM-ALM), which decouples the source of the nerve from the regenerating host environment. Using the NM-ALM we discovered that non-neural extrinsic factors from differently sized host animals do not play a prominent role in determining the size of the regenerating limb. We have also discovered that the regulation of limb size is not autonomously regulated by the limb nerves. Together, these observations show that the limb nerves provide essential and instructive cues to regulate the final size of the regenerating limb.

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