Matthias Krause

Matthias Krause
King's College London | KCL · Randall Division of Cell and Molecular Biophysics

PhD

About

59
Publications
6,408
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4,292
Citations
Introduction
Matthias Krause discovered Lamellipodin, and found that it recruits Ena/VASP proteins to lamellipodia. He started his own group in 2004 at King’s College London, UK, and research from his laboratory has revealed that Lamellipodin controls the actin cytoskeleton during axon morphogenesis, endocytosis of the EGF receptor via Ena/VASP, and cell migration and breast cancer metastasis through a novel interaction with the Scar/WAVE complex. For more information see: www.krauselab.org
Additional affiliations
December 2004 - present
King's College London
July 2000 - November 2004

Publications

Publications (59)
Article
Full-text available
Cell migration is essential for development, but its deregulation causes metastasis. The Scar/WAVE complex is absolutely required for lamellipodia and is a key effector in cell migration, but its regulation in vivo is enigmatic. Lamellipodin (Lpd) controls lamellipodium formation through an unknown mechanism. Here, we report that Lpd directly binds...
Article
Full-text available
Membrane protrusions at the leading edge of cells, known as lamellipodia, drive cell migration in many normal and pathological situations. Lamellipodial protrusion is powered by actin polymerization, which is mediated by the actin-related protein 2/3 (ARP2/3)-induced nucleation of branched actin networks and the elongation of actin filaments. Recen...
Article
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Cancer invasion is a hallmark of metastasis. The mesenchymal mode of cancer cell invasion is mediated by elongated membrane protrusions driven by the assembly of branched F-actin networks. How deregulation of actin regulators promotes cancer cell invasion is still enigmatic. We report that increased expression and membrane localization of the actin...
Article
Full-text available
Cell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex is essential for Arp2/3 mediated lamellipodia formation during mesenchymal cell migration and several coinciding signals activate it. However, so far, no direct negative regulators are known. Here we identify Nance-Horan Syndr...
Article
Full-text available
Glioblastoma is a tumor type of unmet need despite the development of multimodal treatment strategies. The main factors contributing to the poor prognosis of glioblastoma patients are diverse genetic and epigenetic changes driving glioblastoma persistence and recurrence. Complemented are these factors by extracellular cues mediated through cell sur...
Preprint
Full-text available
The RAC1-WAVE-Arp2/3 signaling pathway generates branched actin networks that power lamellipodium protrusion of migrating cells. Feedback is thought to control protrusion lifetime and migration persistence, but its molecular circuitry remains elusive. Using proteomics, we identified PPP2R1A among proteins differentially associated with the WAVE com...
Preprint
Autophagy is essential for neuronal development and its deregulation contributes to neurodegenerative diseases. NDR1 and NDR2 are highly conserved kinases implicated in neuronal development, mitochondrial health and autophagy, but how they affect mammalian brain development in vivo is not known. Using single and double Ndr1/2 knockout mouse models...
Preprint
Phosphoinositides are pivotal regulators of vesicular traffic and signaling during phagocytosis. Phagosome formation, the initial step of the process, is characterized by local membrane remodelling and reorganization of the actin cytoskeleton that leads to formation of the pseudopods that drive particle engulfment. Using genetically-encoded fluores...
Article
Full-text available
Cell cycle control is a key aspect of numerous physiological and pathological processes. The contribution of biophysical cues, such as stiffness or elasticity of the underlying extracellular matrix (ECM), is critically important in regulating cell cycle progression and proliferation. Indeed, increased ECM stiffness causes aberrant cell cycle progre...
Preprint
Full-text available
Cell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex is essential for Arp2/3 mediated lamellipodia formation during mesenchymal cell migration and several coinciding signals activate it. However, so far, no direct negative regulators are known. We have identified Nance-Horan Syn...
Article
Full-text available
Efficient migration on adhesive surfaces involves the protrusion of lamellipodial actin networks and their subsequent stabilization by nascent adhesions. The actin-binding protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin filaments and by in...
Preprint
Full-text available
Efficient migration on adhesive surfaces involves the protrusion of lamellipodial actin networks and their subsequent stabilization by nascent adhesions. The actin binding protein lamellipodin (Lpd) is thought to play a critical role in lamellipodium protrusion, by delivering Ena/VASP proteins onto the growing plus ends of actin filaments and by in...
Article
Full-text available
In the version of this Letter originally published, the name of co-author Safa Lucken-Ardjomande Häsler was coded wrongly, resulting in it being incorrect when exported to citation databases. This has been corrected, though no visible changes will be apparent.
Article
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Endocytosis mediates the cellular uptake of micronutrients and the turnover of plasma membrane proteins. Clathrin-mediated endocytosis is the major uptake pathway in resting cells1, but several clathrin-independent endocytic routes exist in parallel2,3. One such pathway, fast endophilin-mediated endocytosis (FEME), is not constitutive but triggered...
Article
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Neural crest migration is critical to its physiological function. Mechanisms controlling mammalian neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo. Here we report requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest in Xenopus and mouse models. We demonstrate t...
Preprint
Migration of the neural crest lineage is critical to its physiological function. Mechanisms controlling neural crest migration are comparatively unknown, due to difficulties accessing this cell population in vivo . Here, we uncover novel requirements of glycogen synthase kinase 3 (GSK3) in regulating the neural crest. We demonstrate that GSK3 is ty...
Article
Full-text available
Lamellipodin (Lpd) functions as an important signalling integrator downstream of growth factor and axon guidance receptors. Mechanistically, Lpd promotes actin polymerization by interacting with F-actin and the actin e ectors Ena/VASP proteins and the SCAR/WAVE complex. Thereby, Lpd supports lamellipodia protrusion, cell migration and endocytosis....
Data
Video S1: Intravital imaging of ZsGreen-Ctrl-shRNA tumor.? Representative 30 minute time lapse movie from multiphoton imaging of a ZsGreen-Ctrl-shRNA tumor. Cyan= Zsgreen-positive cells, red= collagen fibers. Images were taken every 2 min for 30 min. Video is played at 5 frames per second. Video S2: Intravital imaging of ZsGreen-Lpd-shRNA2 tumor.?...
Article
Full-text available
The epidermal growth factor receptor (EGFR) plays an essential role during development and diseases including cancer. Lamellipodin (Lpd) is known to control lamellipodia protrusion by regulating actin filament elongation via Ena/VASP proteins. However, it is unknown whether this mechanism supports endocytosis of the EGFR. Here, we have identified a...
Article
Full-text available
Mena (mammalian Ena) is an actin regulatory protein involved in cell motility and adhesion. Based on its potential role in malignant transformation revealed in other organs, we analyzed the Mena expression in normal salivary glands (SG) and salivary tumors. Mena expression was determined in normal SG (n=10) and also benign (n=20) and malignant (n=3...
Article
Arrays of transparent rolled-up microtubes can easily be mass-produced using a combination of conventional photolithography, electron beam depositioning, and chemical etching techniques. Here, we culture primary mouse motor neurons and immortalised CAD cells, a cell line derived from the central nervous system, on various microtube substrates to in...
Article
Full-text available
Tight regulation of cell motility is essential for many physiological processes, such as formation of a functional nervous system and wound healing. Drosophila Abl negatively regulates the actin cytoskeleton effector protein Ena during neuronal development in flies, and it has been postulated that this may occur through an unknown intermediary. Lam...
Article
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MIG-10/RIAM/lamellipodin (MRL) proteins link activated Ras-GTPases with actin regulatory Ena/VASP proteins to induce local changes in cytoskeletal dynamics and cell motility. MRL proteins alter monomeric (G):filamentous (F) actin ratios, but the impact of these changes had not been fully appreciated. We report here that the Drosophila MRL ortholog,...
Article
Full-text available
Platelet aggregation requires agonist-induced alphaIIbbeta3 activation, a process mediated by Rap1 and talin. To study mechanisms, we engineered alphaIIbbeta3 Chinese hamster ovary (CHO) cells to conditionally express talin and protease-activated receptor (PAR) thrombin receptors. Human PAR1 or murine PAR4 stimulation activates alphaIIbbeta3, which...
Article
Full-text available
The actin cytoskeleton is required for many important processes during embryonic development. In later stages of life, important homeostatic processes depend on the actin cytoskeleton, such as immune response, haemostasis and blood vessel preservation. Therefore, the function of the actin cytoskeleton must be tightly regulated, and aberrant regulat...
Article
The cytoplasmic C. elegans protein MIG-10 affects cell migrations and is related to mammalian proteins that bind phospholipids and Ena/VASP actin regulators. In cultured cells, mammalian MIG-10 promotes lamellipodial growth and Ena/VASP proteins induce filopodia. We show here that during neuronal development, mig-10 and the C. elegans Ena/VASP homo...
Article
The small GTPase Rap1, originally identified by its ability to reverse Ras-mediated transformation, regulates cytoskeleton organization, adherens junction positioning and cell adhesion. In T cells, Rap1 is activated upon TCR ligation and recruited to the plasma membrane where it regulates activation of β1 (VLA4, VLA5) and β2 (LFA-1) integrins. Howe...
Article
Lamellipodial protrusion is regulated by Ena/VASP proteins. We identified Lamellipodin (Lpd) as an Ena/VASP binding protein. Both proteins colocalize at the tips of lamellipodia and filopodia. Lpd is recruited to EPEC and Vaccinia, pathogens that exploit the actin cytoskeleton for their own motility. Lpd contains a PH domain that binds specifically...
Article
The small GTPase Rap1 induces integrin-mediated adhesion and changes in the actin cytoskeleton. The mechanisms that mediate these effects of Rap1 are poorly understood. We have identified RIAM as a Rap1-GTP-interacting adaptor molecule. RIAM defines a family of adaptor molecules that contain a RA-like (Ras association) domain, a PH (pleckstrin homo...
Article
Ena/VASP proteins play important roles in axon outgrowth and guidance. Ena/VASP activity regulates the assembly and geometry of actin networks within fibroblast lamellipodia. In growth cones, Ena/VASP proteins are concentrated at filopodia tips, yet their role in growth cone responses to guidance signals has not been established. We found that Ena/...
Article
Full-text available
Ena/VASP proteins are a conserved family of actin regulatory proteins made up of EVH1, EVH2 domains, and a proline-rich central region. They have been implicated in actin-based processes such as fibroblast migration, axon guidance, and T cell polarization and are important for the actin-based motility of the intracellular pathogen Listeria monocyto...
Article
Full-text available
Ena/VASP proteins are actin-binding proteins that localize to actin stress fibres, the tips of filopodia and the lamellipodial leading edge. In the past few years, a number of seemingly conflicting studies have confused the Ena/VASP field, pointing to roles for these proteins in both promotion and inhibition of actin-dependent processes. Recent dis...
Article
Ena/VASP proteins are actin-binding proteins that localize to actin stress fibres, the tips of filopodia and the lamellipodial leading edge. In the past few years, a number of seemingly conflicting studies have confused the Ena/VASP field, pointing to roles for these proteins in both promotion and inhibition of actin-dependent processes. Recent dis...
Article
Cell motility requires lamellipodial protrusion, a process driven by actin polymerization. Ena/VASP proteins accumulate in protruding lamellipodia and promote the rapid actin-driven motility of the pathogen Listeria. In contrast, Ena/VASP negatively regulate cell translocation. To resolve this paradox, we analyzed the function of Ena/VASP during la...
Article
Full-text available
Phagocytosis by macrophages and neutrophils involves the spatial and temporal reorganisation of the actin-based cytoskeleton at sites of particle ingestion. Local polymerisation of actin filaments supports the protrusion of pseudopodia that eventually engulf the particle. Here we have investigated in detail the cytoskeletal events initiated upon en...
Article
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Actin polymerization is accompanied by the formation of protein complexes that link extracellular signals to sites of actin assembly such as membrane ruffles and focal adhesions. One candidate recently implicated in these processes is the LIM domain protein zyxin, which can bind both Ena/vasodilator-stimulated phosphoprotein (VASP) proteins and the...
Article
Cellular actin assembly is tightly regulated. The study of pathogen motility has led to the identification of several cellular factors that are critical for controlling this process. Pathogens such as Listeria require Ena/VASP and Arp2/3 proteins to translate actin polymerization into movement. Recent work has extended these observations and uncove...
Article
Full-text available
T cell receptor (TCR)-driven activation of helper T cells induces a rapid polarization of their cytoskeleton towards bound antigen presenting cells (APCs). We have identified the Fyn- and SLP-76-associated protein Fyb/SLAP as a new ligand for Ena/ vasodilator-stimulated phosphoprotein (VASP) homology 1 (EVH1) domains. Upon TCR engagement, Fyb/SLAP...

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