IPP Complex Research Articles

Outside-in & Inside-out Signaling in Integrins: The Key Players in Schwann Cell Biology

Event Abstract Back to Event Outside-in & Inside-out Signaling in Integrins: The Key Players in Schwann Cell Biology Lina Aires1*, Laura Montani1 and Joao B. Relvas1 1 Universidade do Porto, Instituto de Biologia Molecular e Celular (IBMC), Portugal Myelination is essential for the normal development of the nervous system and greatly increases the conduction velocity of the nervous impulse. Control of myelination derives, at least in part, from signals originated within the extracellular environment from which growth factors and proteins of the extracellular matrix (ECM) are essential components.There is a significant body of evidence showing that during peripheral nervous system (PNS) development Schwann cells (SCs) need to interpret different extracellular cues to regulate their migration, proliferation and the remarkable morphological changes associated with myelination of axons. Recruitment of cytoskeleton and signaling molecules to cell matrix contact sites, where they link the actin cytoskeleton to the ECM, mediates signal transduction between the extracellular and the intracellular compartments (outside-in signaling). Among the integrins, the β1-integrin subunit is part of many integrin heterodimers and in Schwann cells the genetic deletion of the β1-integrin subunit gene causes defects in SC- axon contact and impairs the capacity of SCs to extend cytoplasmic processes into embryonic axons bundles to establish one-to-one relationships with individual axons, a process referred to as radial sorting.Our work focus the role of β1-integrins together with its interacting partners of the IPP complex (integrin- linked-kinase, PINCH and Parvin) and different Rho GTPases in Schwann cells biology during the development of the peripheral nervous system.Insights into such mechanisms will hopefully help us to better understanding of myelination and may suggest therapeutic approaches to Peripheral Neuropathies. Conference: 11th Meeting of the Portuguese Society for Neuroscience, Braga, Portugal, 4 Jun - 6 Jun, 2009. Presentation Type: Poster Presentation Topic: Neuronal Communication Citation: Aires L, Montani L and Relvas JB (2009). Outside-in & Inside-out Signaling in Integrins: The Key Players in Schwann Cell Biology. Front. Neurosci. Conference Abstract: 11th Meeting of the Portuguese Society for Neuroscience. doi: 10.3389/conf.neuro.01.2009.11.140 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 11 Aug 2009; Published Online: 11 Aug 2009. * Correspondence: Lina Aires, Universidade do Porto, Instituto de Biologia Molecular e Celular (IBMC), Porto, Portugal, lina.adriana@ibmc.up.pt Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Lina Aires Laura Montani Joao B Relvas Google Lina Aires Laura Montani Joao B Relvas Google Scholar Lina Aires Laura Montani Joao B Relvas PubMed Lina Aires Laura Montani Joao B Relvas Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

Platelet Protein Interactions

Assembly of a comprehensive proteome and transcriptome database of human platelets, derivation of a model of the platelet-specific interactome, and generation of a functional interaction map of platelet phosphorylations and kinases. Interactions are derived from literature-curated data from HPRD and yeast two hybrid (Y2H) and mapped to platelet-specific expression data (SAGE or proteome). From this a cell-type specific model of platelet proteins and protein-protein interactions is derived. The obtained inventory of platelet-specific proteins includes key domains, protein GO annotations, and receptors. Collected interactions point to new platelet signaling components, actin remodeling processes, and pharmacological targets and offer incentives for further studies (eg, on the IPP complex). Integration of platelet-specific phosphoproteins and the characterization of the platelet kinase repertoire sketch a first outline of kinase signaling in human platelets. A first view of the platelet interactome, platelet phosphorylation, and platelet kinome is available from the in silico data.

The Rsu-1-PINCH1-ILK complex is regulated by Ras activation in tumor cells

The link between Ras transformation and enhanced cell migration due to altered integrin signaling is well established in tumorigenesis, however there remain gaps in our understanding of its mechanism. The Ras suppressor, Rsu-1, has recently been linked to the IPP (integrin-linked kinase {ILK}, PINCH-1/LIMS1, parvin) focal adhesion complex based on its interaction with the LIM 5 domain of PINCH1. Defining the role of the Rsu1-PINCH1-ILK-parvin complex in tumorigenesis is important because both ILK and PINCH1 are elevated in certain tumors while ectopic expression of Rsu-1 blocks tumorigenesis. Our studies previously identified an alternatively spliced isoform of Rsu-1 in high-grade gliomas. We report here the detection of a truncated (p29) Rsu-1 protein, which correlates with the presence of the alternatively spliced Rsu-1 RNA. This RNA and the respective protein were detected in human tumor cell lines that contain high levels of activated Ras, and inhibitor studies demonstrate that the Mek-ERK pathway regulates expression of this truncated Rsu-1 product. We also show that Rsu-1 co-localizes with ILK at focal contacts and co-immunoprecipitates with the ILK-PINCH1 complex in non-transformed cells, but following Ras transformation the association of Rsu-1 with the PINCH1-ILK complex is greatly reduced. Using a human breast cancer cell line, our in vitro studies demonstrate that the depletion of Rsu-1 full-length protein enhances cell migration coincident with an increase in Rac-GTP while the depletion of the p29 Rsu-1 truncated protein inhibits migration. These findings indicate that Rsu-1 may inhibit cell migration by stabilizing the IPP adhesion complex and that Ras activation perturbs this inhibitory function by modulating both Rsu-1 splicing and association of full-length Rsu-1 with IPP. Hence, our findings demonstrate that Rsu-1 links the Ras pathway with the IPP complex and the perturbations of cell attachment-dependent signaling that occur in the malignant process.

Assembly of an in silico model of the platelet interactome and in vitro validation of IPP complex interactions of human platelets

Assembly of an in silico model of the platelet interactome and in vitro validation of IPP complex interactions of human platelets