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Phospho-Drosophila Akt (Ser505) Antibody

RRID:AB_331414

Antibody ID

AB_331414

Target Antigen

Phospho-Drosophila Akt (Ser505) See NCBI gene drosophila melanogaster

Proper Citation

(Cell Signaling Technology Cat# 4054, RRID:AB_331414)

Clonality

polyclonal antibody

Comments

Applications: W

Host Organism

rabbit

Vendor

Cell Signaling Technology

The Drosophila Immune Deficiency Pathway Modulates Enteroendocrine Function and Host Metabolism.

  • Kamareddine L
  • Cell Metab.
  • 2018 Jun 15

Literature context:


Abstract:

Enteroendocrine cells (EEs) are interspersed between enterocytes and stem cells in the Drosophila intestinal epithelium. Like enterocytes, EEs express components of the immune deficiency (IMD) innate immune pathway, which activates transcription of genes encoding antimicrobial peptides. The discovery of large lipid droplets in intestines of IMD pathway mutants prompted us to investigate the role of the IMD pathway in the host metabolic response to its intestinal microbiota. Here we provide evidence that the short-chain fatty acid acetate is a microbial metabolic signal that activates signaling through the enteroendocrine IMD pathway in a PGRP-LC-dependent manner. This, in turn, increases transcription of the gene encoding the endocrine peptide Tachykinin (Tk), which is essential for timely larval development and optimal lipid metabolism and insulin signaling. Our findings suggest innate immune pathways not only provide the first line of defense against infection but also afford the intestinal microbiota control over host development and metabolism.

Funding information:
  • NIAID NIH HHS - R01 AI019018(United States)
  • NIAID NIH HHS - R01 AI071147()
  • NIAID NIH HHS - R21 AI109436()

Elevated Levels of the Reactive Metabolite Methylglyoxal Recapitulate Progression of Type 2 Diabetes.

  • Moraru A
  • Cell Metab.
  • 2018 Apr 3

Literature context:


Abstract:

The molecular causes of type 2 diabetes (T2D) are not well understood. Both type 1 diabetes (T1D) and T2D are characterized by impaired insulin signaling and hyperglycemia. From analogy to T1D, insulin resistance and hyperglycemia are thought to also play causal roles in T2D. Recent clinical studies, however, found that T2D patients treated to maintain glycemia below the diabetes definition threshold (HbA1c < 6.5%) still develop diabetic complications. This suggests additional insulin- and glucose-independent mechanisms could be involved in T2D progression and/or initiation. T2D patients have elevated levels of the metabolite methylglyoxal (MG). We show here, using Drosophila glyoxalase 1 knockouts, that animals with elevated methylglyoxal recapitulate several core aspects of T2D: insulin resistance, obesity, and hyperglycemia. Thus elevated MG could constitute one root cause of T2D, suggesting that the molecular causes of elevated MG warrant further study.

Funding information:
  • NIAID NIH HHS - R01AI100934(United States)

The InR/Akt/TORC1 Growth-Promoting Signaling Negatively Regulates JAK/STAT Activity and Migratory Cell Fate during Morphogenesis.

  • Kang D
  • Dev. Cell
  • 2018 Feb 26

Literature context:


Abstract:

Cell growth and cell differentiation are two distinct yet coupled developmental processes, but how they are coordinated is not well understood. During Drosophila oogenesis, we found that the growth-promoting InR/Akt/TOR pathway was involved in suppressing the fate determination of the migratory border cells. The InR/Akt/TOR pathway signals through TOR and Raptor, components of TORC1, to downregulate the JAK/STAT pathway, which is necessary and sufficient for border cell fate determination. TORC1 promotes the protein stability of SOCS36E, the conserved negative regulator of JAK/STAT signaling, through physical interaction, suggesting that TORC1 acts as a key regulator coordinating both cell growth and cell differentiation.

Funding information:
  • Canadian Institutes of Health Research - (Canada)

Inter-adipocyte Adhesion and Signaling by Collagen IV Intercellular Concentrations in Drosophila.

  • Dai J
  • Curr. Biol.
  • 2017 Sep 25

Literature context:


Abstract:

Sheet-forming Collagen IV is the main component of basement membranes, which are planar polymers of extracellular matrix underlying epithelia and surrounding organs in all animals. Adipocytes in both insects and mammals are mesodermal in origin and often classified as mesenchymal. However, they form true tissues where cells remain compactly associated. Neither the mechanisms providing this tissue-level organization nor its functional significance are known. Here we show that discrete Collagen IV intercellular concentrations (CIVICs), distinct from basement membranes and thicker in section, mediate inter-adipocyte adhesion in Drosophila. Loss of these Collagen-IV-containing structures in the larval fat body caused intercellular gaps and disrupted continuity of the adipose tissue layer. We also found that Integrin and Syndecan matrix receptors attach adipocytes to CIVICs and direct their formation. Finally, we show that Integrin-mediated adhesion to CIVICs promotes normal adipocyte growth and prevents autophagy through Src-Pi3K-Akt signaling. Our results evidence a surprising non-basement membrane role of Collagen IV in non-epithelial tissue morphogenesis while demonstrating adhesion and signaling functions for these structures.

Muscle Directs Diurnal Energy Homeostasis through a Myokine-Dependent Hormone Module in Drosophila.

  • Zhao X
  • Curr. Biol.
  • 2017 Jul 10

Literature context:


Abstract:

Inter-tissue communication is critical to control organismal energy homeostasis in response to temporal changes in feeding and activity or external challenges. Muscle is emerging as a key mediator of this homeostatic control through consumption of lipids, carbohydrates, and amino acids, as well as governing systemic signaling networks. However, it remains less clear how energy substrate usage tissues, such as muscle, communicate with energy substrate storage tissues in order to adapt with diurnal changes in energy supply and demand. Using Drosophila, we show here that muscle plays a crucial physiological role in promoting systemic synthesis and accumulation of lipids in fat storage tissues, which subsequently impacts diurnal changes in circulating lipid levels. Our data reveal that the metabolic transcription factor Foxo governs expression of the cytokine unpaired 2 (Upd2) in skeletal muscle, which acts as a myokine to control glucagon-like adipokinetic hormone (AKH) secretion from specialized neuroendocrine cells. Circulating AKH levels in turn regulate lipid homeostasis in fat body/adipose and the intestine. Our data also reveal that this novel myokine-dependent hormone module is critical to maintain diurnal rhythms in circulating lipids. This tissue crosstalk provides a putative mechanism that allows muscle to integrate autonomous energy demand with systemic energy storage and turnover. Together, these findings reveal a diurnal inter-tissue signaling network between muscle and fat storage tissues that constitutes an ancestral mechanism governing systemic energy homeostasis.

Funding information:
  • NIDDK NIH HHS - R01 DK108930()

Fluorescein Isothiocyanate (FITC)-Dextran Extravasation as a Measure of Blood-Brain Barrier Permeability.

  • Natarajan R
  • Curr Protoc Neurosci
  • 2017 Apr 10

Literature context:


Abstract:

The blood-brain barrier (BBB) is formed in part by vascular endothelial cells that constitute the capillaries and microvessels of the brain. The function of this barrier is to maintain homeostasis within the brain microenvironment and buffer the brain from changes in the periphery. A dysfunction of the BBB would permit circulating molecules and pathogens typically restricted to the periphery to enter the brain and interfere with normal brain function. As increased permeability of the BBB is associated with several neuropathologies, it is important to have a reliable and sensitive method that determines BBB permeability and the degree of BBB disruption. A detailed protocol is presented for assessing the integrity of the BBB by transcardial perfusion of a 10,000 Da FITC-labeled dextran molecule and its visualization to determine the degree of extravasation from brain microvessels. © 2017 by John Wiley & Sons, Inc.

Funding information:
  • NIDA NIH HHS - R01 DA007606()
  • NIDA NIH HHS - R01 DA035499()

The Ubiquitin Ligase CHIP Integrates Proteostasis and Aging by Regulation of Insulin Receptor Turnover.

  • Tawo R
  • Cell
  • 2017 Apr 20

Literature context:


Abstract:

Aging is attended by a progressive decline in protein homeostasis (proteostasis), aggravating the risk for protein aggregation diseases. To understand the coordination between proteome imbalance and longevity, we addressed the mechanistic role of the quality-control ubiquitin ligase CHIP, which is a key regulator of proteostasis. We observed that CHIP deficiency leads to increased levels of the insulin receptor (INSR) and reduced lifespan of worms and flies. The membrane-bound INSR regulates the insulin and IGF1 signaling (IIS) pathway and thereby defines metabolism and aging. INSR is a direct target of CHIP, which triggers receptor monoubiquitylation and endocytic-lysosomal turnover to promote longevity. However, upon proteotoxic stress conditions and during aging, CHIP is recruited toward disposal of misfolded proteins, reducing its capacity to degrade the INSR. Our study indicates a competitive relationship between proteostasis and longevity regulation through CHIP-assisted proteolysis, providing a mechanistic concept for understanding the impact of proteome imbalance on aging.

Insulin signaling controls neurotransmission via the 4eBP-dependent modification of the exocytotic machinery.

  • Mahoney RE
  • Elife
  • 2016 Aug 15

Literature context:


Abstract:

Altered insulin signaling has been linked to widespread nervous system dysfunction including cognitive dysfunction, neuropathy and susceptibility to neurodegenerative disease. However, knowledge of the cellular mechanisms underlying the effects of insulin on neuronal function is incomplete. Here, we show that cell autonomous insulin signaling within the Drosophila CM9 motor neuron regulates the release of neurotransmitter via alteration of the synaptic vesicle fusion machinery. This effect of insulin utilizes the FOXO-dependent regulation of the thor gene, which encodes the Drosophila homologue of the eif-4e binding protein (4eBP). A critical target of this regulatory mechanism is Complexin, a synaptic protein known to regulate synaptic vesicle exocytosis. We find that the amounts of Complexin protein observed at the synapse is regulated by insulin and genetic manipulations of Complexin levels support the model that increased synaptic Complexin reduces neurotransmission in response to insulin signaling.