Profilin 1–mediated cytoskeletal rearrangements regulate integrin function in mouse platelets

Stritt, Simon; Birkholz, Inga; Beck, Sarah; Sorrentino, Simona; Sapra, K. Tanuj; Viaud, Julien; Heck, Johannes; Gaits‐Iacovoni, Frédérique; Schulze, Harald; Du, Xiaoping; Hartwig, John H.; Braun, Attila; Bender, Markus; Medalia, Ohad; Nieswandt, Bernhard

doi:10.1182/bloodadvances.2017014001

Cited by 9 publications

(19 citation statements)

References 24 publications

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“…Profilin 1 is a member of profilin family of small ABP, which ubiquitously expressed in various types of cells ( Rodriguez Del Rio et al, 2018 ). Profilin 1 played an important role in regulation of actin polymerization and cytoskeleton remodeling ( Stritt et al, 2018 ). Serum profilin 1 was independently associated with endothelial dysfunction, cardiovascular events and survival in patients with chronic kidney disease ( Eroglu et al, 2017 ; Li X. et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Protein Tyrosine Phosphatase Receptor S Acts as a Metastatic Suppressor in Malignant Peripheral Nerve Sheath Tumor via Profilin 1-Induced Epithelial-Mesenchymal Transition

Ren

Cui

et al. 2020

Front. Cell Dev. Biol.

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Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas with over half of cases developed in the context of neurofibromatosis type 1. Surgical resection is the only effective therapy for MPNST. The prognosis is very dismal once recurrence or metastasis occurs. Epithelial-mesenchymal transition (EMT) is a key process of recurrence and metastasis involving reorganizations of the actin cytoskeleton and actin-binding proteins (ABP) play a non-negligible role. Protein tyrosine phosphatase receptor S (PTPRS), a tumor suppressor previously reported in colorectal cancer, hepatocellular carcinoma and head and neck cancer, is thought to mediate cell migration and invasion by downregulation of EMT. However, its role in MPNST remains unknown. In the present study, by using tissue microarray we demonstrated low expression of PTPRS was related to poor prognosis in MPNST. Knockdown of PTPRS in MPNST cell lines increased migration/invasion and EMT processes were induced with increased N-cadherin and decreased E-cadherin, which indicated PTPRS may serve as a tumor suppressor in MPNST. In addition, we tested all EMT related ABP and found profilin 1 was significantly elevated in PTPRS downregulated MPNST cell lines. As a member of actin-binding proteins, profilins are regulators of actin polymerization and contribute to cell motility and invasion, which have been reported to be responsible for EMT. Moreover, results showed that downregulation of profilin 1 could restore the EMT processes caused by PTPRS downregulation in vitro and in vivo . Furthermore, high expression of profilin 1 was significantly associated with dismal prognosis. These results highlighted PTPRS served as a potential tumor suppressor in the recurrence and metastasis of MPNST via profilin 1 induced EMT processes and it might provide potential targets for future clinical therapeutics.

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Section: Discussionmentioning

confidence: 99%

Protein Tyrosine Phosphatase Receptor S Acts as a Metastatic Suppressor in Malignant Peripheral Nerve Sheath Tumor via Profilin 1-Induced Epithelial-Mesenchymal Transition

Ren

Cui

et al. 2020

Front. Cell Dev. Biol.

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“…Washed platelets were prepared as described previously (58). Briefly, mice were anesthetized using isoflurane and bled into 300 μL heparin (20 U/mL in TBS, Ratiopharm).…”

Section: Mouse Platelet Preparationmentioning

confidence: 99%

“…Tail bleeding time and in vivo thrombus formation studies in the mechanically injured abdominal aorta were performed as described elsewhere (58).…”

Section: Tail Bleeding Time and In Vivo Thrombus Formationmentioning

confidence: 99%

“…Then, 24 hours later, infarct sizes were analyzed in brain sections by TTC staining. Histology and IHC were performed according Immunoblotting Western blot analysis was performed as described previously (58). Untreated or activated platelets were lysed at the respective time points, separated by SDS-PAGE, and blotted on a PVDF membrane, on which the proteins were detected using anti-BIN2 antibody (Proteintech, 14245-1-AB), anti-STIM1 antibody (Cell Signaling Technology, 4916), anti-IP 3 R antibody (Merck-Millipore, 07-1210), anti-RhoA (Cytoskeleton, ARH04), and anti-GAPDH (MilliporeSigma, G9545).…”

Section: Tail Bleeding Time and In Vivo Thrombus Formationmentioning

confidence: 99%

“…Flow cytometry to determine glycoprotein expression, integrin activation, and P-selectin exposure was performed as previously described (58). In short, heparinized whole blood was diluted 1:20 in Tyrode's HEPES buffer.…”

Section: Flow Cytometrymentioning

confidence: 99%

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BIN2 orchestrates platelet calcium signaling in thrombosis and thrombo-inflammation

Volz¹,

Kusch²,

Beck³

et al. 2020

Journal of Clinical Investigation

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A Multi-omics Longitudinal Study Reveals Alteration of the Leukocyte Activation Pathway in COVID-19 Patients

et al. 2021

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Severe coronavirus disease 2019 (COVID-19) infection may lead to lung injury, multi-organ failure, and eventually death. Cytokine storm due to excess cytokine production has been associated with fatality in severe infections. However, the specific molecular signatures associated with the elevated immune response are yet to be elucidated. We performed a mass-spectrometry-based proteomic and metabolomic analysis of COVID-19 plasma samples collected at two time points. Using Orbitrap Fusion LC–MS/MS-based label-free proteomic analysis, we identified around 10 significant proteins, 32 significant peptides, and 5 metabolites that were dysregulated at the severe time points. Few of these proteins identified by quantitative proteomics were validated using the multiple reaction monitoring (MRM) assay. Integrated pathway analysis using distinct proteomic and metabolomic signatures revealed alterations in complement and coagulation cascade, platelet aggregation, myeloid leukocyte activation pathway, and arginine metabolism. Further, we highlight the role of leukocyte activation and arginine metabolism in COVID-19 pathogenesis and targeting these pathways for COVID-19 therapeutics.

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Profilin 1–mediated cytoskeletal rearrangements regulate integrin function in mouse platelets

Abstract: Key Points Profilin 1–mediated cytoskeletal dynamics regulate platelet β1- and β3-integrin function and turnover. Profilin 1 deficiency in platelets impairs hemostasis and results in a marked protection from arterial thrombosis.

Cited by 9 publications

References 24 publications

Protein Tyrosine Phosphatase Receptor S Acts as a Metastatic Suppressor in Malignant Peripheral Nerve Sheath Tumor via Profilin 1-Induced Epithelial-Mesenchymal Transition

Protein Tyrosine Phosphatase Receptor S Acts as a Metastatic Suppressor in Malignant Peripheral Nerve Sheath Tumor via Profilin 1-Induced Epithelial-Mesenchymal Transition

BIN2 orchestrates platelet calcium signaling in thrombosis and thrombo-inflammation

A Multi-omics Longitudinal Study Reveals Alteration of the Leukocyte Activation Pathway in COVID-19 Patients

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