scholarly journals Faculty Opinions recommendation of Lsm12 is an NAADP receptor and a two-pore channel regulatory protein required for calcium mobilization from acidic organelles.

2021 ◽  
Author(s):  
Antony Galione ◽  
Anthony John Morgan
Keyword(s):  
Regulatory Protein ◽  
Calcium Mobilization ◽  
Pore Channel ◽  
Acidic Organelles

scholarly journals Lsm12 is an NAADP receptor and a two-pore channel regulatory protein required for calcium mobilization from acidic organelles

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Jiyuan Zhang ◽  
Xin Guan ◽  
Kunal Shah ◽  
Jiusheng Yan
Keyword(s):  
Molecular Basis ◽  
Rna Binding ◽  
Affinity Purification ◽  
Regulatory Protein ◽  
Rna Binding Protein ◽  
Pore Channel ◽  
Interacting Proteins ◽  
Molecular Identity ◽  
Acidic Organelles ◽  
Apparent Association

AbstractNicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+-mobilizing second messenger which uniquely mobilizes Ca2+ from acidic endolysosomal organelles. However, the molecular identity of the NAADP receptor remains unknown. Given the necessity of the endolysosomal two-pore channel (TPC1 or TPC2) in NAADP signaling, we performed affinity purification and quantitative proteomic analysis of the interacting proteins of NAADP and TPCs. We identified a Sm-like protein Lsm12 complexed with NAADP, TPC1, and TPC2. Lsm12 directly binds to NAADP via its Lsm domain, colocalizes with TPC2, and mediates the apparent association of NAADP to isolated TPC2 or TPC2-containing membranes. Lsm12 is essential and immediately participates in NAADP-evoked TPC activation and Ca2+ mobilization from acidic stores. These findings reveal a putative RNA-binding protein to function as an NAADP receptor and a TPC regulatory protein and provides a molecular basis for understanding the mechanisms of NAADP signaling.

scholarly journals Lsm12 is an NAADP receptor and a two-pore channel regulatory protein required for calcium mobilization from acidic organelles

2020 ◽  
Author(s):  
Jiyuan Zhang ◽  
Xin Guan ◽  
Jiusheng Yan
Keyword(s):  
Proteomic Analysis ◽  
Molecular Basis ◽  
Rna Binding ◽  
Affinity Purification ◽  
Regulatory Protein ◽  
Rna Binding Protein ◽  
Pore Channel ◽  
Interacting Proteins ◽  
Molecular Identity ◽  
Acidic Organelles

SUMMARYNicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+-mobilizing second messenger which uniquely mobilizes Ca2+ from acidic endolysosomal organelles. However, the molecular identity of the NAADP receptor remains unknown. Given the necessity of the endolysosomal two-pore channel (TPC1 or TPC2) in NAADP signaling, we performed affinity purification and quantitative proteomic analysis of the interacting proteins of NAADP and TPCs. We identified an Sm-like protein Lsm12 complexed with NAADP, TPC1, and TPC2. Lsm12 directly binds to NAADP via its Lsm domain, whereas TPC-containing membranes and isolated TPCs lose their affinities to NAADP in the absence of Lsm12. Lsm12 is essential and directly involved in NAADP-evoked TPC2 activation and Ca2+ mobilization. These findings reveal a putative RNA-binding protein to function as an NAADP receptor and a TPC regulatory protein and provides a molecular basis for understanding the mechanisms of NAADP signaling.

scholarly journals A plastid two-pore channel essential for inter-organelle communication and growth of Toxoplasma gondii

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Zhu-Hong Li ◽  
Thayer P. King ◽  
Lawrence Ayong ◽  
Beejan Asady ◽  
Xinjiang Cai ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Lytic Cycle ◽  
Site Formation ◽  
Pore Channel ◽  
Apicomplexan Parasites ◽  
Unicellular Organisms ◽  
Membrane Contact ◽  
Organelle Communication ◽  
Acidic Organelles ◽  
Pore Lining

AbstractTwo-pore channels (TPCs) are a ubiquitous family of cation channels that localize to acidic organelles in animals and plants to regulate numerous Ca2+-dependent events. Little is known about TPCs in unicellular organisms despite their ancient origins. Here, we characterize a TPC from Toxoplasma gondii, the causative agent of toxoplasmosis. TgTPC is a member of a novel clad of TPCs in Apicomplexa, distinct from previously identified TPCs and only present in coccidians. We show that TgTPC localizes not to acidic organelles but to the apicoplast, a non-photosynthetic plastid found in most apicomplexan parasites. Conditional silencing of TgTPC resulted in progressive loss of apicoplast integrity, severely affecting growth and the lytic cycle. Isolation of TPC null mutants revealed a selective role for TPCs in replication independent of apicoplast loss that required conserved residues within the pore-lining region. Using a genetically-encoded Ca2+ indicator targeted to the apicoplast, we show that Ca2+ signals deriving from the ER but not from the extracellular space are selectively transmitted to the lumen. Deletion of the TgTPC gene caused reduced apicoplast Ca2+ uptake and membrane contact site formation between the apicoplast and the ER. Fundamental roles for TPCs in maintaining organelle integrity, inter-organelle communication and growth emerge.

scholarly journals Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) Induces Intracellular Ca2+ Release through the Two-Pore Channel TPC1 in Metastatic Colorectal Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 542 ◽  
Author(s):  
Pawan Faris ◽  
Giorgia Pellavio ◽  
Federica Ferulli ◽  
Francesca Di Nezza ◽  
Mudhir Shekha ◽  
...  
Keyword(s):  
Nicotinic Acid ◽  
Primary Cultures ◽  
Calf Serum ◽  
Release Mechanism ◽  
Pore Channel ◽  
Genetic Manipulations ◽  
Extracellular Signal ◽  
Colorectal Cancer Cells ◽  
Novel Target ◽  
Acidic Organelles

Nicotinic acid adenine dinucleotide phosphate (NAADP) gates two-pore channels 1 and 2 (TPC1 and TPC2) to elicit endo-lysosomal (EL) Ca2+ release. NAADP-induced EL Ca2+ signals may be amplified by the endoplasmic reticulum (ER) through the Ca2+-induced Ca2+ release mechanism (CICR). Herein, we aimed at assessing for the first time the role of EL Ca2+ signaling in primary cultures of human metastatic colorectal carcinoma (mCRC) by exploiting Ca2+ imaging and molecular biology techniques. The lysosomotropic agent, Gly-Phe β-naphthylamide (GPN), and nigericin, which dissipates the ΔpH which drives Ca2+ refilling of acidic organelles, caused massive Ca2+ release in the presence of a functional inositol-1,4,5-trisphosphate (InsP3)-sensitive ER Ca2+ store. Liposomal delivery of NAADP induced a transient Ca2+ release that was reduced by GPN and NED-19, a selective TPC antagonist. Pharmacological and genetic manipulations revealed that the Ca2+ response to NAADP was triggered by TPC1, the most expressed TPC isoform in mCRC cells, and required ER-embedded InsP3 receptors. Finally, NED-19 and genetic silencing of TPC1 reduced fetal calf serum-induced Ca2+ signals, proliferation, and extracellular signal-regulated kinase and Akt phoshorylation in mCRC cells. These data demonstrate that NAADP-gated TPC1 could be regarded as a novel target for alternative therapies to treat mCRC.

scholarly journals Pertussis toxin does not inhibit muscarinic-receptor-mediated phosphoinositide hydrolysis or calcium mobilization

1985 ◽  
Vol 227 (3) ◽  
pp. 933-937 ◽  
Author(s):  
S B Masters ◽  
M W Martin ◽  
T K Harden ◽  
J H Brown
Keyword(s):  
Muscarinic Receptor ◽  
Muscarinic Receptors ◽  
Pertussis Toxin ◽  
Inositol Phosphate ◽  
Regulatory Protein ◽  
Calcium Mobilization ◽  
Phosphoinositide Hydrolysis ◽  
Heart Cells ◽  
Chick Heart ◽  
Stimulation Of

Pertussis toxin was used to examine the role of the inhibitory guanine nucleotide regulatory protein, Ni, in muscarinic-receptor-mediated stimulation of phosphoinositide turnover and calcium mobilization. In cultured chick heart cells, pertussis-toxin treatment inhibited muscarinic-receptor-mediated attenuation of isoprenaline-stimulated cyclic AMP accumulation. This finding is consistent with the proposal that pertussis toxin blocks the capacity of Ni to couple muscarinic receptors to adenylate cyclase. In contrast, treatment of chick heart cells or 1321N1 human astrocytoma cells with pertussis toxin did not block muscarinic-receptor-mediated stimulation of phosphoinositide hydrolysis, as measured by [3H]inositol phosphate accumulation in the presence of Li+. Pertussis-toxin treatment also had little effect on basal and muscarinic-receptor-stimulated phosphatidylinositol synthesis, as measured by the incorporation of [3H]inositol into phosphatidylinositol. Activation of muscarinic receptors also enhances the rate of unidirectional 45Ca2+ efflux in 1321N1 cells; this response, like phosphoinositide hydrolysis, was not prevented by pertussis-toxin treatment. Our data suggest that muscarinic receptors are not coupled to phosphoinositide hydrolysis or calcium mobilization through Ni.

scholarly journals Two-pore Channels for Calcium Mobilization from Acidic Organelles and Cell Signaling by NAADP

2009 ◽  
Vol 96 (3) ◽  
pp. 391a
Author(s):  
Peter J. Calcraft ◽  
Abdelilah Arredouani ◽  
Zui Pan ◽  
Xiaotong Cheng ◽  
Jisen Tang ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Calcium Mobilization ◽  
Acidic Organelles

The N-terminal region of two-pore channel 1 regulates trafficking and activation by NAADP

2013 ◽  
Vol 453 (1) ◽  
pp. 147-151 ◽  
Author(s):  
Dev Churamani ◽  
Robert Hooper ◽  
Taufiq Rahman ◽  
Eugen Brailoiu ◽  
Sandip Patel
Keyword(s):  
Endoplasmic Reticulum ◽  
Ion Channels ◽  
Nicotinic Acid ◽  
Subcellular Location ◽  
Dual Role ◽  
Terminal Region ◽  
Pore Channel ◽  
N Terminus ◽  
And Function ◽  
Acidic Organelles

TPCs (two-pore channels) are NAADP (nicotinic acid–adenine dinucleotide phosphate)-sensitive Ca2+-permeable ion channels expressed on acidic organelles. In the present study we show that deletion of the N-terminal region redirects TPC1 to the ER (endoplasmic reticulum). The introduction of fluorophores at the N-terminus of TPC1 does not affect its subcellular location, but does reversibly abolish NAADP sensitivity. Our results reveal a dual role for the N-terminus in localization and function of TPC1.

Von Hermaphroditos der griechischen Mythologie bis zu DSD der Moderne

Praxis ◽  
2008 ◽  
Vol 98 (1) ◽  
pp. 31-34
Author(s):  
Oestmann ◽  
Mullis ◽  
Stanga
Keyword(s):  
Regulatory Protein ◽  
Steroidogenic Acute Regulatory Protein ◽  
Sich Eine ◽  
Fand Sich ◽  
Steroidogenic Acute Regulatory

Wir berichten über eine heute 34-jährige Frau, die im Alter von 6 Monaten wegen rezidivierendem Erbrechen hospitalisiert werden musste. Als Ursache fand sich eine Nebenniereninsuffizienz mit Verminderung sämtlicher Hormone der Steroidhormonbiosynthese. Die weiteren Abklärungen ergaben bei dem phänotypisch weiblichen Säugling eine lipoide kongenitale adrenale Hyperplasie mit 46,XY DSD. 24 Jahre später konnte in der DNS-Sequenzanalyse ein homozygoter, in der Schweiz vorkommender Basenaustausch des steroidogenic acute regulatory protein-Gens gefunden werden, welcher zu einem Aminosäurenaustausch Leucin 260 Prolin (L260P) führt.

Influence of increased nutrient supply on Microcystis aeruginosa at cellular and proteomic levels

2020 ◽  
Vol 85 ◽  
pp. 47-58
Author(s):  
Y Jiang ◽  
Y Liu
Keyword(s):  
Microcystis Aeruginosa ◽  
Regulatory Protein ◽  
Acid Synthesis ◽  
Nutrient Supply ◽  
Nitrogen Supply ◽  
Nitrogen And Phosphorus ◽  
Comprehensive Description ◽  
Amino Acid Synthesis ◽  
High Nutrient ◽  
Proteomic Responses

Various studies have observed that increased nutrient supply promotes the growth of bloom-forming cyanobacteria, but only a limited number of studies have investigated the influence of increased nutrient supply on bloom-forming cyanobacteria at the proteomic level. We investigated the cellular and proteomic responses of Microcystis aeruginosa to elevated nitrogen and phosphorus supply. Increased supply of both nutrients significantly promoted the growth of M. aeruginosa and the synthesis of chlorophyll a, protein, and microcystins. The release of microcystins and the synthesis of polysaccharides negatively correlated with the growth of M. aeruginosa under high nutrient levels. Overexpressed proteins related to photosynthesis, and amino acid synthesis, were responsible for the stimulatory effects of increased nutrient supply in M. aeruginosa. Increased nitrogen supply directly promoted cyanobacterial growth by inducing the overexpression of the cell division regulatory protein FtsZ. NtcA, that regulates gene transcription related to both nitrogen assimilation and microcystin synthesis, was overexpressed under the high nitrogen condition, which consequently induced overexpression of 2 microcystin synthetases (McyC and McyF) and promoted microcystin synthesis. Elevated nitrogen supply induced the overexpression of proteins involved in gas vesicle organization (GvpC and GvpW), which may increase the buoyancy of M. aeruginosa. Increased phosphorus level indirectly affected growth and the synthesis of cellular substances in M. aeruginosa through the mediation of differentially expressed proteins related to carbon and phosphorus metabolism. This study provides a comprehensive description of changes in the proteome of M. aeruginosa in response to an increased supply of 2 key nutrients.

Evidence against a gonadotropin-induced regulatory protein in mouse Leydig cells

1988 ◽  
Vol 117 (4_Suppl) ◽  
pp. S70-S71
Author(s):  
M. SCHUMACHER ◽  
J. LUDOLPH ◽  
F. LEIDENBERGER
Keyword(s):  
Leydig Cells ◽  
Regulatory Protein
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