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20170712-Leslie-3 - A molecular switch orchestrates enzyme specificity and secretory granule morphology

ABSTRACT: 190 proteins were identified from three samples. Among them41 proteins were detected in sample Layer 1 and/or Layer 2 but not in sample Layer 3, and one protein (SPCS2) was detected all three samples but its relative abundance is higher in Layer 1 than that in Layer 3. These 42 proteins can be considered as the most possible candidates proteins which are specifically present in the secretory granules prepared in this experiment.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Drosophila Melanogaster (fruit Fly)

TISSUE(S): Salivary Gland

SUBMITTER: Xianglin Zhai

LAB HEAD: Alex Zhai

PROVIDER: PXD010549 | Pride | 2019-04-03

REPOSITORIES: Pride

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			Action	DRS
	20170712-Leslie-3.mzid.gz	Mzid
	20170712-Leslie-3.pride.mztab.gz	Mztab
	Leslie-Band3.raw	Raw
	My Experiment.mzid.gz_20170712-Leslie-3.pride.mgf.gz	Mzid
	MyExperiment.mzid.gz_20170712-Leslie-3.MGF	Mzid

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Publications

A molecular switch orchestrates enzyme specificity and secretory granule morphology.

Ji Suena S Samara Nadine L NL Revoredo Leslie L Zhang Liping L Tran Duy T DT Muirhead Kayla K Tabak Lawrence A LA Ten Hagen Kelly G KG

Nature communications 20180829 1

Regulated secretion is an essential process where molecules destined for export are directed to membranous secretory granules, where they undergo packaging and maturation. Here, we identify a gene (pgant9) that influences the structure and shape of secretory granules within the Drosophila salivary gland. Loss of pgant9, which encodes an O-glycosyltransferase, results in secretory granules with an irregular, shard-like morphology, and altered glycosylation of cargo. Interestingly, pgant9 undergoe ...[more]

PMID: 30158631

Similar Datasets

Project title: 20170712-Leslie-1

Project description:190 proteins were identified from three samples. Among them41 proteins were detected in sample Layer 1 and/or Layer 2 but not in sample Layer 3, and one protein (SPCS2) was detected all three samples but its relative abundance is higher in Layer 1 than that in Layer 3. These 42 proteins can be considered as the most possible candidates proteins which are specifically present in the secretory granules prepared in this experiment.

2018-10-16 | PXD010548 | Pride

A molecular switch orchestrates enzyme specificity and secretory granule morphology.

Project description:Regulated secretion is an essential process where molecules destined for export are directed to membranous secretory granules, where they undergo packaging and maturation. Here, we identify a gene (pgant9) that influences the structure and shape of secretory granules within the Drosophila salivary gland. Loss of pgant9, which encodes an O-glycosyltransferase, results in secretory granules with an irregular, shard-like morphology, and altered glycosylation of cargo. Interestingly, pgant9 undergoes a splicing event that acts as a molecular switch to alter the charge of a loop controlling access to the active site of the enzyme. The splice variant with the negatively charged loop glycosylates the positively charged secretory cargo and rescues secretory granule morphology. Our study highlights a mechanism for dictating substrate specificity within the O-glycosyltransferase enzyme family. Moreover, our in vitro and in vivo studies suggest that the glycosylation status of secretory cargo influences the morphology of maturing secretory granules.

| S-EPMC6115407 | biostudies-literature

Gene expression of cerebellar granule cell layer

Project description:We performed gene-expression analysis of mouse cerebellar granule cell layer as compared to that of Purkinje cells. DNA microarray analysis detected genes in cerebellar granule cell layer, most of which are classified into functional molecule categories. Our comparative analysis between Purkinje cells and the granule cell layer showed that the characteristic expression pattern in Purkinje cells was particularly represented by M-bM-^@M-^\the neural communication systemM-bM-^@M-^] components. Pukinje cells and granule cell layer of the mouse cerebellum were collected by laser microdissection for RNA extraction and hybridization on Affymetrix microarrays.

2013-01-17 | E-GEOD-26750 | biostudies-arrayexpress

Gene expression of cerebellar granule cell layer

2013-01-17 | GSE26750 | GEO

Chimp 190 biopsy baseline vs post infection

Project description:Transcriptional profiling of chimp 190 liver biopsy comparing baseline sample with biopsy taken different days after innoculation with HCV Keywords: Genetic modification

2008-04-10 | GSE11104 | GEO

GSK-3β orchestrates the inhibitory innervation of adult-born dentate granule cells in vivo.

Project description:Adult hippocampal neurogenesis enhances brain plasticity and contributes to the cognitive reserve during aging. Adult hippocampal neurogenesis is impaired in neurological disorders, yet the molecular mechanisms regulating the maturation and synaptic integration of new neurons have not been fully elucidated. GABA is a master regulator of adult and developmental neurogenesis. Here we engineered a novel retrovirus encoding the fusion protein Gephyrin:GFP to longitudinally study the formation and maturation of inhibitory synapses during adult hippocampal neurogenesis in vivo. Our data reveal the early assembly of inhibitory postsynaptic densities at 1 week of cell age. Glycogen synthase kinase 3 Beta (GSK-3β) emerges as a key regulator of inhibitory synapse formation and maturation during adult hippocampal neurogenesis. GSK-3β-overexpressing newborn neurons show an increased number and altered size of Gephyrin+ postsynaptic clusters, enhanced miniature inhibitory postsynaptic currents, shorter and distanced axon initial segments, reduced synaptic output at the CA3 and CA2 hippocampal regions, and impaired pattern separation. Moreover, GSK-3β overexpression triggers a depletion of Parvalbumin+ interneuron perineuronal nets. These alterations might be relevant in the context of neurological diseases in which the activity of GSK-3β is dysregulated.

| S-EPMC10363517 | biostudies-literature

Single-stranded DNA orchestrates an ATM-to-ATR switch at DNA breaks.

Project description:ATM and ATR are two master checkpoint kinases activated by double-stranded DNA breaks (DSBs). ATM is critical for the initial response and the subsequent ATR activation. Here we show that ATR activation is coupled with loss of ATM activation, an unexpected ATM-to-ATR switch during the biphasic DSB response. ATM is activated by DSBs with blunt ends or short single-stranded overhangs (SSOs). Surprisingly, the activation of ATM in the presence of SSOs, like that of ATR, relies on single- and double-stranded DNA junctions. In a length-dependent manner, SSOs attenuate ATM activation and potentiate ATR activation through a swap of DNA-damage sensors. Progressive resection of DSBs directly promotes the ATM-to-ATR switch in vitro. In cells, the ATM-to-ATR switch is driven by both ATM and the nucleases participating in DSB resection. Thus, single-stranded DNA orchestrates ATM and ATR to function in an orderly and reciprocal manner in two distinct phases of DSB response.

| S-EPMC2675165 | biostudies-literature

Macrophage phenotypic switch orchestrates the inflammation and repair/regeneration following acute pancreatitis injury.

Project description:BackgroundImpaired or hyperactive pancreas regeneration after injury would cause exocrine insufficiency or recurrent / chronic pancreatitis and potentially carcinogenesis. Macrophages are the most abundant immune cells in the regenerative pancreas, however their phenotype and role remain poorly defined.MethodUsing caerulein-induced acute pancreatitis (AP) model, we examined the dynamic landscape of pancreatic macrophages throughout the acute inflammation to regeneration phases by flow cytometric and RNA-seq analyses. Liposome depletion of macrophages, Il4ra-/- mice as well as inhibitors were used to elucidate the role and regulatory mechanism of macrophages during pancreatic regeneration.FindingsWe found that M1 macrophages dominated in the pro-inflammatory phase of AP, while M2-like macrophages dominated during pancreas repair/regeneration. Depletion of macrophages at early or late regenerative stage dramatically blocked the acinar-ductal metaplasia (ADM) or delayed inflammation resolution, respectively. Moreover, alternative activation of macrophages was partially dependent on IL-4RA signaling, and ECM/AKT activation in pancreatic macrophages facilitated inflammation resolution during tissue regeneration.InterpretationOur findings illustrate a dynamic phenotype and function of macrophages during AP repair/regeneration, helping us better understand the mechanism of pancreatic regeneration and providing clues for novel therapeutic strategy.

| S-EPMC7399125 | biostudies-literature

single cell RNA-seq from cerebellar granule layer (ENCSR822EWO)

Project description:LCMD-503,504_Mm_Castaneus_x_C57Bl-granule-layer-area-dissection For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODE_Data_Use_Policy_for_External_Users_03-07-14.pdf

2016-11-08 | GSE88567 | GEO

Dendritic morphology and inhibitory regulation distinguish dentate semilunar granule cells from granule cells through distinct stages of postnatal development.

Project description:Semilunar granule cells (SGCs) have been proposed as a morpho-functionally distinct class of hippocampal dentate projection neurons contributing to feedback inhibition and memory processing in juvenile rats. However, the structural and physiological features that can reliably classify granule cells (GCs) from SGCs through postnatal development remain unresolved. Focusing on postnatal days 11-13, 28-42, and > 120, corresponding with human infancy, adolescence, and adulthood, we examined the somato-dendritic morphology and inhibitory regulation in SGCs and GCs to determine the cell-type specific features. Unsupervised cluster analysis confirmed that morphological features reliably distinguish SGCs from GCs irrespective of animal age. SGCs maintain higher spontaneous inhibitory postsynaptic current (sIPSC) frequency than GCs from infancy through adulthood. Although sIPSC frequency in SGCs was particularly enhanced during adolescence, sIPSC amplitude and cumulative charge transfer declined from infancy to adulthood and were not different between GCs and SGCs. Extrasynaptic GABA current amplitude peaked in adolescence in both cell types and was significantly greater in SGCs than in GCs only during adolescence. Although GC input resistance was higher than in SGCs during infancy and adolescence, input resistance decreased with developmental age in GCs, while it progressively increased in SGCs. Consequently, GCs' input resistance was significantly lower than SGCs in adults. The data delineate the structural features that can reliably distinguish GCs from SGCs through development. The results reveal developmental differences in passive membrane properties and steady-state inhibition between GCs and SGCs which could confound their use in classifying the cell types.

| S-EPMC7677165 | biostudies-literature

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