scholarly journals Cdc42-dependent leading edge coordination is essential for interstitial dendritic cell migration

Blood ◽  
2009 ◽  
Vol 113 (23) ◽  
pp. 5703-5710 ◽  
Author(s):  
Tim Lämmermann ◽  
Jörg Renkawitz ◽  
Xunwei Wu ◽  
Karin Hirsch ◽  
Cord Brakebusch ◽  
...  
Keyword(s):  
Specific Interaction ◽  
Leading Edge ◽  
Small Gtpase ◽  
3 Dimensional ◽  
Dendritic Cell Migration ◽  
Adhesive Interactions ◽  
Actomyosin Contraction ◽  
Extracellular Environment ◽  
Pericellular Proteolysis

Abstract Mature dendritic cells (DCs) moving from the skin to the lymph node are a prototypic example of rapidly migrating amoeboid leukocytes. Interstitial DC migration is directionally guided by chemokines, but independent of specific adhesive interactions with the tissue as well as pericellular proteolysis. Instead, the protrusive flow of the actin cytoskeleton directly drives a basal mode of locomotion that is occasionally supported by actomyosin contractions at the trailing edge to propel the cell's rigid nucleus. We here delete the small GTPase Cdc42 in DCs and find that actin flow and actomyosin contraction are still initiated in response to chemotactic cues. Accordingly, the cells are able to polarize and form protrusions. However, in the absence of Cdc42 the protrusions are temporally and spatially dysregulated, which leads to impaired leading edge coordination. Although this defect still allows the cells to move on 2-dimensional surfaces, their in vivo motility is completely abrogated. We show that this difference is entirely caused by the geometric complexity of the environment, as multiple competing protrusions lead to instantaneous entanglement within 3-dimensional extracellular matrix scaffolds. This demonstrates that the decisive factor for migrating DCs is not specific interaction with the extracellular environment, but adequate coordination of cytoskeletal flow.

scholarly journals Rab7b regulates dendritic cell migration by linking lysosomes to the actomyosin cytoskeleton

2021 ◽  
Author(s):  
Katharina Vestre ◽  
Irene Persiconi ◽  
Marita Borg Distefano ◽  
Nadia Mensali ◽  
Noemi Antonella Guadagno ◽  
...  
Keyword(s):  
Cell Migration ◽  
Immune Cell ◽  
Myosin Ii ◽  
Small Gtpase ◽  
Peripheral Tissues ◽  
3 Dimensional ◽  
Late Endosomes ◽  
Dendritic Cell Migration ◽  
Transcription Factor Eb ◽  
Actomyosin Cytoskeleton

Lysosomal signaling facilitates the migration of immune cells by releasing calcium to activate the actin-based motor myosin II at the cell rear. However, how the actomyosin cytoskeleton physically associates to lysosomes is unknown. We have previously identified myosin II as a direct interactor of Rab7b, a small GTPase that mediates the transport from late endosomes/lysosomes to the TGN. Here, we show that Rab7b regulates the migration of dendritic cells (DCs) in 1- and 3-dimensional environments. DCs are immune sentinels that transport antigens from peripheral tissues to lymph nodes to activate T lymphocytes and initiate adaptive immune responses. We found that lack of Rab7b reduces myosin II light chain phosphorylation and the activation of the transcription factor EB (TFEB), which controls lysosomal signaling and is required for fast DC migration. Furthermore, we demonstrate that Rab7b interacts with the lysosomal calcium channel TRPML1, enabling the local activation of myosin II at the cell rear. Altogether, our findings identify Rab7b as the missing physical link between lysosomes and the actomyosin cytoskeleton, allowing control of immune cell migration through lysosomal signaling.

scholarly journals Preformed portals facilitate dendritic cell entry into afferent lymphatic vessels

2009 ◽  
Vol 206 (13) ◽  
pp. 2925-2935 ◽  
Author(s):  
Holger Pflicke ◽  
Michael Sixt
Keyword(s):  
Lymphatic Vessels ◽  
Intercellular Junctions ◽  
Cell Entry ◽  
Common Assumption ◽  
Imaging Approach ◽  
Leukocyte Extravasation ◽  
Adhesive Interactions ◽  
Extracellular Environment ◽  
Pericellular Proteolysis

Although both processes occur at similar rates, leukocyte extravasation from the blood circulation is well investigated, whereas intravasation into lymphatic vessels has hardly been studied. In contrast to a common assumption—that intra- and extravasation follow similar molecular principles—we previously showed that lymphatic entry of dendritic cells (DCs) does not require integrin-mediated adhesive interactions. In this study, we demonstrate that DC-entry is also independent of pericellular proteolysis, raising the question of whether lymphatic vessels offer preexisting entry routes. We find that the perilymphatic basement membrane of initial lymphatic vessels is discontinuous and therefore leaves gaps for entering cells. Using a newly developed in situ live cell imaging approach that allows us to dynamically visualize the cells and their extracellular environment, we demonstrate that DCs enter through these discontinuities, which are transiently mechanically dilated by the passaging cells. We further show that penetration of the underlying lymphatic endothelial layer occurs through flap valves lacking continuous intercellular junctions. Together, we demonstrate free cellular communication between interstitium and lymphatic lumen.

42-OR: Hub Cells Orchestrate 3-Dimensional Pancreatic Beta-Cell Ca2+ Dynamics In Vivo

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 42-OR
Author(s):  
VICTORIA SALEM ◽  
LUIS F. DELGADILLO SILVA ◽  
KINGA SUBA ◽  
ALDARA MARTIN ALONSO ◽  
WHEI-CHANG KIM ◽  
...  
Keyword(s):  
Beta Cell ◽  
Pancreatic Beta Cell ◽  
3 Dimensional

Correlation between in vitro and in vivo Data of Radiolabeled Peptide for Tumor Targeting

2019 ◽  
Vol 19 (12) ◽  
pp. 950-960
Author(s):  
Soghra Farzipour ◽  
Seyed Jalal Hosseinimehr
Keyword(s):  
Tumor Targeting ◽  
Single Photon ◽  
Specific Binding ◽  
Specific Interaction ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Mixed Effect ◽  
Radiolabeled Peptides

Tumor-targeting peptides have been generally developed for the overexpression of tumor specific receptors in cancer cells. The use of specific radiolabeled peptide allows tumor visualization by single photon emission computed tomography (SPECT) and positron emission tomography (PET) tools. The high affinity and specific binding of radiolabeled peptide are focusing on tumoral receptors. The character of the peptide itself, in particular, its complex molecular structure and behaviors influence on its specific interaction with receptors which are overexpressed in tumor. This review summarizes various strategies which are applied for the expansion of radiolabeled peptides for tumor targeting based on in vitro and in vivo specific tumor data and then their data were compared to find any correlation between these experiments. With a careful look at previous studies, it can be found that in vitro unblock-block ratio was unable to correlate the tumor to muscle ratio and the success of radiolabeled peptide for in vivo tumor targeting. The introduction of modifiers’ approaches, nature of peptides, and type of chelators and co-ligands have mixed effect on the in vitro and in vivo specificity of radiolabeled peptides.

scholarly journals An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marisa Nacke ◽  
Emma Sandilands ◽  
Konstantina Nikolatou ◽  
Álvaro Román-Fernández ◽  
Susan Mason ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Cellular Responses ◽  
Signalling Pathways ◽  
External Signal ◽  
Phosphoinositide Metabolism ◽  
Invasion And Metastasis ◽  
3 Dimensional

AbstractThe signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P3 production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PI(3,4,5)P3 signalling, and predicts long-term poor outcome across multiple cancers. IQSEC1-regulated phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis.

scholarly journals A Region of the Myosin Rod Important for Interaction With Paramyosin in Caenorhabditis elegans Striated Muscle

Genetics ◽  
2000 ◽  
Vol 156 (2) ◽  
pp. 631-643
Author(s):  
Pamela E Hoppe ◽  
Robert H Waterston
Keyword(s):  
Caenorhabditis Elegans ◽  
Heavy Chain ◽  
Molecular Interaction ◽  
Striated Muscle ◽  
Genetic Interaction ◽  
Specific Interaction ◽  
Thick Filament ◽  
Parallel Arrangement ◽  
Myosin Rod

Abstract The precise arrangement of molecules within the thick filament, as well as the mechanisms by which this arrangement is specified, remains unclear. In this article, we have exploited a unique genetic interaction between one isoform of myosin heavy chain (MHC) and paramyosin in Caenorhabditis elegans to probe the molecular interaction between MHC and paramyosin in vivo. Using chimeric myosin constructs, we have defined a 322-residue region of the MHC A rod critical for suppression of the structural and motility defects associated with the unc-15(e73) allele. Chimeric constructs lacking this region of MHC A either fail to suppress, or act as dominant enhancers of, the e73 phenotype. Although the 322-residue region is required for suppression activity, our data suggest that sequences along the length of the rod also play a role in the isoform-specific interaction between MHC A and paramyosin. Our genetic and cell biological analyses of construct behavior suggest that the 322-residue region of MHC A is important for thick filament stability. We present a model in which this region mediates an avid interaction between MHC A and paramyosin in parallel arrangement in formation of the filament arms.

scholarly journals Meyer’s Loop Anatomy Demonstrated Using Diffusion Tensor MR Imaging and Fiber Tractography at 3T

2014 ◽  
Vol 60 (5) ◽  
pp. 215-222 ◽  
Author(s):  
Cristina Goga ◽  
Zeynep Firat ◽  
Klara Brinzaniuc ◽  
Is Florian
Keyword(s):  
Diffusion Tensor Imaging ◽  
Diffusion Tensor ◽  
Region Of Interest ◽  
Fiber Tractography ◽  
Brain Images ◽  
3 Dimensional ◽  
Software Release ◽  
Magnetic Resonance Imaging Mri ◽  
Meyer’S Loop

Abstract Objective: The ultimate anatomy of the Meyer’s loop continues to elude us. Diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) may be able to demonstrate, in vivo, the anatomy of the complex network of white matter fibers surrounding the Meyer’s loop and the optic radiations. This study aims at exploring the anatomy of the Meyer’s loop by using DTI and fiber tractography. Methods: Ten healthy subjects underwent magnetic resonance imaging (MRI) with DTI at 3 T. Using a region-of-interest (ROI) based diffusion tensor imaging and fiber tracking software (Release 2.6, Achieva, Philips), sequential ROI were placed to reconstruct visual fibers and neighboring projection fibers involved in the formation of Meyer’s loop. The 3-dimensional (3D) reconstructed fibers were visualized by superimposition on 3-planar MRI brain images to enhance their precise anatomical localization and relationship with other anatomical structures. Results: Several projection fiber including the optic radiation, occipitopontine/parietopontine fibers and posterior thalamic peduncle participated in the formation of Meyer’s loop. Two patterns of angulation of the Meyer’s loop were found. Conclusions: DTI with DTT provides a complimentary, in vivo, method to study the details of the anatomy of the Meyer’s loop.

scholarly journals Micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and secretion to improve osseointegration

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Zhengchuan Zhang ◽  
Ruogu Xu ◽  
Yang Yang ◽  
Chaoan Liang ◽  
Xiaolin Yu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Titanium Surface ◽  
Titanium Implants ◽  
Extracellular Secretion ◽  
Exosome Biogenesis ◽  
Marrow Mesenchymal Stem Cells ◽  
Proliferation In Vitro ◽  
Extracellular Environment

Abstract Background Micro/nano-textured hierarchical titanium topography is more bioactive and biomimetic than smooth, micro-textured or nano-textured titanium topographies. Bone marrow mesenchymal stem cells (BMSCs) and exosomes derived from BMSCs play important roles in the osseointegration of titanium implants, but the effects and mechanisms of titanium topography on BMSCs-derived exosome secretion are still unclear. This study determined whether the secretion behavior of exosomes derived from BMSCs is differently affected by different titanium topographies both in vitro and in vivo. Results We found that both micro/nanonet-textured hierarchical titanium topography and micro/nanotube-textured hierarchical titanium topography showed favorable roughness and hydrophilicity. These two micro/nano-textured hierarchical titanium topographies enhanced the spreading areas of BMSCs on the titanium surface with stronger promotion of BMSCs proliferation in vitro. Compared to micro-textured titanium topography, micro/nano-textured hierarchical titanium topography significantly enhanced osseointegration in vivo and promoted BMSCs to synthesize and transport exosomes and then release these exosomes into the extracellular environment both in vitro and in vivo. Moreover, micro/nanonet-textured hierarchical titanium topography promoted exosome secretion by upregulating RAB27B and SMPD3 gene expression and micro/nanotube-textured hierarchical titanium topography promoted exosome secretion due to the strongest enhancement in cell proliferation. Conclusions These findings provide evidence that micro/nano-textured hierarchical titanium topography promotes exosome biogenesis and extracellular secretion for enhanced osseointegration. Our findings also highlight that the optimized titanium topography can increase exosome secretion from BMSCs, which may promote osseointegration of titanium implants.

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