VASP

Last update 23 Jan 2025

Basic Info

Synonyms

vasodilator stimulated phosphoprotein, Vasodilator-stimulated phosphoprotein, VASP

Introduction

Ena/VASP proteins are actin-associated proteins involved in a range of processes dependent on cytoskeleton remodeling and cell polarity such as axon guidance, lamellipodial and filopodial dynamics, platelet activation and cell migration. VASP promotes actin filament elongation. It protects the barbed end of growing actin filaments against capping and increases the rate of actin polymerization in the presence of capping protein. VASP stimulates actin filament elongation by promoting the transfer of profilin-bound actin monomers onto the barbed end of growing actin filaments. Plays a role in actin-based mobility of Listeria monocytogenes in host cells. Regulates actin dynamics in platelets and plays an important role in regulating platelet aggregation.

100 Clinical Results associated with VASP

100 Translational Medicine associated with VASP

0 Patents (Medical) associated with VASP

1,502

Literatures (Medical) associated with VASP

01 Mar 2025·Cellular Signalling

Platelet inhibition by hypochlorous acid involves cAMP signalling

Article

Author: Smolenski, Albert ; Hiebner, Dishon ; Krishnankutty, Roopesh ; Schoen, Ingmar ; O'Donoghue, Lorna ; von Kriegsheim, Alex

Hypochlorous acid (HOCl), made by neutrophil-derived myeloperoxidase, has been suggested to inhibit platelets, however, the mechanisms involved have not been described. Here we confirm that HOCl exposure changes platelet morphology and inhibits platelet spreading and aggregation. HOCl effects could be reversed by glutathione suggesting a role for cysteine oxidation. Mass spectrometry-based proteomics of HOCl-exposed platelets revealed oxidised cysteine residues in 37 proteins including adenylate cyclase 6 and Rap1B. Adenylate cyclase is involved in the inhibitory cAMP pathway triggered by endothelium-derived prostacyclin and Rap1 is a small G protein required for integrin αIIbβ3 activation and platelet aggregation. We show that HOCl exposure stimulates cAMP production and phosphorylation of the cAMP-dependent protein kinase substrate VASP in platelets and transfected HEK293T cells. In addition, HOCl inhibited Rap1-GTP formation. These data suggest that HOCl inhibits platelets at least in part through the cAMP pathway and by regulating Rap1. Thus, this study provides new insights into HOCl mediated crosstalk between neutrophils and platelets.

01 Jan 2025·Experimental Neurology

DDAH1 deficiency exacerbates cerebral vascular endothelial dysfunction by aggravating BBB disruption and oxidative stress in thoracic blast-induced brain injury

Article

Author: Hou, Mingxiao ; Mao, Shun ; Tong, Changci ; Cong, Peifang ; Liu, Yunen ; Shi, Lin

As terrorist incidents and underground explosion events have become more frequent around the world, brain injury caused by thoracic blast exposure has been more highlighted due to its injured organ, subsequent social and economic burden. It has been reported dimethylarginine dimethylaminohydrolase 1 (DDAH1) plays important roles in regulating vascular endothelial injury repair and angiogenesis, but its role in thoracic blast-induced brain injury remains to be explained. This study seeks to investigate the mechanism of DDAH1 on thoracic blast-induced brain injury. 40 C57BL/6 wild type mice and 40 DDAH1 knockout mice were randomly and equally divided into control group and blast group, respectively. The integrity of blood-brain barrier (BBB) was detected by Evans blue test. The serum inflammatory factors, nitric oxide (NO) contents, and asymmetric dimethylarginine (ADMA) levels were determined through ELISA. HE staining and reactive oxygen species (ROS) detection were performed for histopathological changes. Western blot was used to detect the proteins related to oxidative stress, tight junction, focal adhesion, vascular endothelial injury, and the DDAH1/ADMA/eNOS signaling pathway. DDAH1 deficiency aggravated thoracic blast-induced BBB leakage, inflammatory response, and the increased levels of inflammatory-related factors. Additionally, DDAH1 deficiency also increased ROS generation, MDA and IRE-α expression. Regarding cerebral vascular endothelial dysfunction, DDAH1 deficiency increased the expression of MCAM, FN1, LIMK1, VEGF, MMP9, Vimentin and N-cadherin, while lowering the expression of FMR1, Occludin, claudin-3, claudin-5, Lyn, LIMA1, Glrb, Sez6, Dystrophin, and phosphorylation of VASP. Also, DDAH1 deficiency exacerbated explosion-induced increase of ADMA and decrease of eNOS activity and NO contents. Thus, we conclude that DDAH1 could prevent cerebral vascular endothelial dysfunction and related injury by inhibiting ADMA signaling and increasing eNOS activity in thoracic blast induced brain injury.

01 Jan 2025·Cellular and Molecular Gastroenterology and Hepatology

PKMζ, a Brain-specific PKCζ Isoform, is Required for Glycolysis and Myofibroblastic Activation of Hepatic Stellate Cells

Article

Author: Wang, Tian ; Bai, Bing ; Wang, Xianghu ; Kitange, Gaspar J ; Kitange, Gaspar J. ; Shaha, Aurpita ; Bao, Wenming ; Kang, Ningling ; Wang, Yuanguo ; He, Lianping

BACKGROUND & AIMSTransforming growth factor (TGF)β1 induces plasma membrane (PM) accumulation of glucose transporter 1 (Glut1) required for glycolysis of hepatic stellate cells (HSCs) and HSC activation. This study aimed to understand how Glut1 is anchored/docked onto the PM of HSCs.METHODSHSC expression of protein kinase M zeta isoform (PKMζ) was detected by reverse transcription polymerase chain reaction (RT-PCR), Western blotting, and immunofluorescence. PKMζ level was manipulated by short hairpin RNA (shRNA) or overexpression; HSC activation was assessed by cell expression of activation markers; PM Glut1, glucose uptake, and glycolysis of HSCs were analyzed by biotinylation, 2-NBDG-based assay, and Seahorse Glycolysis Stress Test. Phospho-mutants of vasodilator-stimulated phosphorylated protein (VASP) were created by site-directed mutagenesis. TGFβ transcriptome was obtained by RNA sequencing. Single-cell RNA sequencing datasets and immunofluorescence were leveraged to analyze PKMζ expression in cancer-associated fibroblasts (CAFs) of colorectal liver metastases. Function of HSC PKMζ was determined by tumor/HSC co-implantation study.RESULTSPrimary human and murine HSCs express PKMζ, but not full-length PKCζ. PKMζ knockdown suppresses, whereas PKMζ overexpression potentiates PM accumulation of Glut1, glycolysis, and HSC activation induced by TGFβ1. Mechanistically, PKMζ binds to and induces VASP phosphorylation at serines 157 and 239 facilitating anchoring/docking of Glut1 onto the PM of HSCs. PKMζ expression is increased in the CAFs of murine and patient colorectal liver metastases compared with quiescent HSCs. Targeting PKMζ suppresses transcriptome, CAF activation of HSCs, and colorectal tumor growth in mice.CONCLUSIONSBecause HSCs are also a major contributor of liver fibrosis, our data highlight PKMζ and VASP as targets to inhibit metabolic reprogramming, HSC activation, liver fibrosis, and the pro-metastatic microenvironment of the liver.

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