<i>In vitro</i> characterization of native mammalian smooth-muscle protein synaptopodin 2

Schroeter, Mechthild M.; Beall, Brent; Heid, Hans; Chalovich, Joseph M.

doi:10.1042/bsr20080079

Cited by 13 publications

(12 citation statements)

References 30 publications

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“…In regard to nicotine, Phox2A regulates transcription of the α3 nAChR gene (69), but its role in the pancreas has not yet been elucidated. SYNPO2 has actin-binding activity and shuttles between the nucleus and the cytoplasm in a stress-induced manner (70). This protein has been studied in neurons, but no evidence is available supporting its function in the pancreas.…”

Section: Resultsmentioning

confidence: 99%

Global Analysis of Protein Expression and Phosphorylation Levels in Nicotine-Treated Pancreatic Stellate Cells

2015

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Smoking is a risk factor in pancreatic disease, however, the biochemical mechanisms correlating smoking with pancreatic dysfunction remain poorly understood. Strategies using multiplexed isobaric tag-based mass spectrometry facilitate the study of drug-induced perturbations on biological systems. Here, we present the first large scale analysis of the proteomic and phosphoproteomic alterations in pancreatic stellate cells following treatment with two nicotinic acetylcholine receptor (nAChR) ligands: nicotine and α-bungarotoxin. We treated cells with nicotine or α-bungarotoxin for 12hr in triplicate and compared alterations in protein expression and phosphorylation levels to mock treated cells using a tandem mass tag (TMT9plex)-based approach. Over 8,100 proteins were quantified across all nine samples of which 46 were altered in abundance upon treatment with nicotine. Proteins with increased abundance included those associated with neurons, defense mechanisms, indicators of pancreatic disease and lysosomal proteins. In addition, we measured differences for ∼16,000 phosphorylation sites across all nine samples using a titanium dioxide-based strategy, of which 132 sites were altered with nicotine and 451 with α-bungarotoxin treatment. Many altered phosphorylation sites were involved in nuclear function and transcriptional events. This study supports the development of future targeted investigations to establish a better understanding for the role of nicotine and associated receptors in pancreatic disease.

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Section: Resultsmentioning

confidence: 99%

Global Analysis of Protein Expression and Phosphorylation Levels in Nicotine-Treated Pancreatic Stellate Cells

2015

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“…Here, the analysis revealed additional genes that had not previously been associated with atherosclerosis, of which several were selected for replication in a nonoverlapping set of patients. LMOD1 (Leiomodin 1) has been predicted to be an SMC-specific gene [64] and an SRF/ MYOCD-dependent transcript [65] and SYNPO2 (Synaptopodin 2) was predicted to be associated with SMC cytoskeletal organization [66]. Because LMOD1 and SYNPO2 were strongly downregulated in plaques and correlated with all markers of differentiated SMCs, they may represent novel markers of SMC phenotype and should be explored in the context of SMC function in atherosclerosis.…”

Section: Discussionmentioning

confidence: 99%

Gene expression signatures, pathways and networks in carotid atherosclerosis

et al. 2015

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Our findings confirmed a central role for inflammation and proteases in plaque instability, and highlighted haemoglobin metabolism and bone resorption as important pathways. Subgroup analysis suggested prolonged inflammation following the symptoms of plaque instability and calcification as a possible stabilizing mechanism by statins. In addition, transcriptional regulation may play an important role in the determination of plaque phenotype. The results from this study will serve as a basis for further exploration of molecular signatures in carotid atherosclerosis.

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“…Subsequent in vitro studies indicated that avian myopodin accelerates actin nucleation, polymerization and bundling (18–20), that rabbit myopodin promotes actin polymerization (21), and that human myopodin can directly bundle actin filaments (9). While these in vitro studies implicated human myopodin as a potential regulator of the actin cytoskeleton, there was no direct evidence in support of this conjecture.…”

Section: Discussionmentioning

confidence: 99%

“…Lastly, the nomenclature in the field has become confusing. Myopodin has variously been referred to as fesselin (2), genethonin (3), myopodin (1, 4, 8, 39) and, more recently, synaptopodin 2 (21). All of these studies refer to the ΔN‐MYO1 isoform in the present report.…”

Section: Discussionmentioning

confidence: 99%

Prostate cancer cell migration induced by myopodin isoforms is associated with formation of morphologically and biochemically distinct actin networks

Kai

Duncan

2013

FASEB j.

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Myopodin is an actin-binding protein that promotes cancer cell migration in response to serum stimulation and is associated with invasive tumor development. To determine whether enhanced migration reflects changes in actin cytoskeleton remodeling, fluorescence confocal microscopy was used to examine the composition and morphology of filamentous actin structures in mock-transduced cells vs. stably transduced PC3 cells expressing human myopodin isoforms, and the chemokinetic response of cells was quantified using transwell assays. The same approaches were used to analyze the effects of external migration stimuli, actin polymerization inhibitors or deletion of the isoform-specific amino- and/or carboxy termini on cell migration and actin bundle formation. Results indicate that the termini of the myopodin isoforms differentially alter the formation of morphologically distinct F-actin networks that also differ in their myosin and myopodin staining patterns. Furthermore, enhanced cell migration was reduced by >50% when actin bundle formation was impaired by myopodin-truncation, low concentrations of an actin polymerization inhibitor, or in the absence of an external migration stimulus. Human myopodin isoforms are therefore potent regulators of stress fiber formation, inducing the formation of biochemically and morphologically distinct F-actin networks in the cell body whose presence directly correlates with increased cell migration.

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In vitro characterization of native mammalian smooth-muscle protein synaptopodin 2

Cited by 13 publications

References 30 publications

Global Analysis of Protein Expression and Phosphorylation Levels in Nicotine-Treated Pancreatic Stellate Cells

Global Analysis of Protein Expression and Phosphorylation Levels in Nicotine-Treated Pancreatic Stellate Cells

Gene expression signatures, pathways and networks in carotid atherosclerosis

Prostate cancer cell migration induced by myopodin isoforms is associated with formation of morphologically and biochemically distinct actin networks

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