Protein Kinase D1 and the β1 Integrin Cytoplasmic Domain Control β1 Integrin Function via Regulation of Rap1 Activation

Medeiros, Ricardo B.; Dickey, Deborah M.; Chung, Hyun Kee; Quale, Angie C.; Nagarajan, Lakshmi; Billadeau, Daniel D.; Shimizu, Yoji

doi:10.1016/j.immuni.2005.07.006

Cited by 77 publications

(97 citation statements)

References 55 publications

(2 reference statements)

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“…This applies more mechanical force on ligandbound integrins at the plasma membrane and results in conformational changes in the integrin that trigger an increase in outside-in signaling. As a result of outside-in signaling, Rap1 is activated, which can increase integrin trafficking to the membrane and leads to a higher rate of integrin exocytosis (Caswell and Norman, 2006;Medeiros et al, 2005). The increased number of activated integrins also slows down integrin endocytosis, perhaps because active integrins are sorted to the slower cycling endosomal compartments and the rate of integrin endocytosis decreases (Arjonen et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

In vivo regulation of integrin turnover by outside-in activation

López-Ceballos

Herrera-Reyes

Coombs

et al. 2016

Journal of Cell Science

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The development of three-dimensional tissue architecture requires precise control over the attachment of cells to the extracellular matrix (ECM). Integrins, the main ECM-binding receptors in animals, are regulated in multiple ways to modulate cell-ECM adhesion. One example is the conformational activation of integrins by extracellular signals ('outside-in activation') or by intracellular signals ('inside-out activation'), whereas another is the modulation of integrin turnover. We demonstrate that outside-in activation regulates integrin turnover to stabilize tissue architecture in vivo. Treating Drosophila embryos with Mg 2+ and Mn 2+, known to induce outside-in activation, resulted in decreased integrin turnover. Mathematical modeling combined with mutational analysis provides mechanistic insight into the stabilization of integrins at the membrane. We show that as tissues mature, outside-in activation is crucial for regulating the stabilization of integrin-mediated adhesions. This data identifies a new in vivo role for outside-in activation and sheds light on the key transition between tissue morphogenesis and maintenance.

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Section: Discussionmentioning

confidence: 99%

In vivo regulation of integrin turnover by outside-in activation

López-Ceballos

Herrera-Reyes

Coombs

et al. 2016

Journal of Cell Science

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“…Motility depends on the ability of cells to assume a ''motile'' form, including reorganization of actin cytoskeleton and possibly alterations of adhesion molecules. Rap1 is a potent activator of integrins and has been shown to induce cell polarization, cell surface receptor redistribution, and migration (3,32,37,38). Rac1 is important for actin reorganization and cell protrusion (39)(40)(41)(42)(43).…”

Section: Discussionmentioning

confidence: 99%

MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo

Fischer

Jacovetty

Medeiros

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The role continuous contact with self-peptide/MHC molecules (self ligands) in the periphery plays in the function of mature T cells remains unclear. Here, we elucidate a role for MHC class II molecules in T cell trafficking and antigen responsiveness in vivo. We find that naïve CD4 T cells deprived of MHC class II molecules demonstrate a progressive and profound defect in motility (measured by real-time two-photon imaging) and that these cells have a decreased ability to interact with limiting numbers of cognate antigen-bearing dendritic cells, but they do not demonstrate a defect in their responsiveness to direct stimulation with anti-CD3 monoclonal antibody. Using GST fusion proteins, we show that MHC class II availability promotes basal activation of Rap1 and Rac1 but does not alter the basal activity of Ras. We propose that tonic T cell receptor signaling from self-ligand stimulation is required to maintain a basal state of activation of small guanosine triphosphatases critical for normal T cell motility and that T cell motility is critical for the antigen receptivity of naïve CD4 T cells. These studies suggest a role for continuous self-ligand stimulation in the periphery for the maintenance and function of mature naïve CD4 T cells.GTPases ͉ MHC class II deficiency ͉ self ligand

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“…Thus, there may be similarities between lymphocytes and platelets in the choice of pathways that lead to Rap1 activation that results in integrin activation. A downstream effector of PKC that leads to Rap1 activation is proposed to be protein kinase D1 The cell biology of leukocyte integrins (KPCD1; also known as PKD1, PKCμ), which forms a complex independently of its kinase activity, together with Rap1 and the β1-integrin cytoplasmic domain, redistributing Rap1 to the membrane (Medeiros et al, 2005).…”

Section: Activation Of Integrins By Inside-out Signallingmentioning

confidence: 99%

Integrins in immunity

Evans

Patzak

Svensson

et al. 2009

Journal of Cell Science

261

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A successful immune response depends on the capacity of immune cells to travel from one location in the body to another–these cells are rapid migrators, travelling at speeds of μm/minute. Their ability to penetrate into tissues and to make contacts with other cells depends chiefly on the β2 integrin known as LFA-1. For this reason, we describe the control of its activity in some detail. For the non-immunologist, the fine details of an immune response often seem difficult to fathom. However, the behaviour of immune cells, known as leukocytes (Box 1), is subject to the same biological rules as many other cell types, and this holds true particularly for the functioning of the integrins on these cells. In this Commentary, we highlight, from a cell-biology point of view, the integrin-mediated immune-cell migration and cell-cell interactions that occur during the course of an immune response.

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Protein Kinase D1 and the β1 Integrin Cytoplasmic Domain Control β1 Integrin Function via Regulation of Rap1 Activation

Cited by 77 publications

References 55 publications

In vivo regulation of integrin turnover by outside-in activation

In vivo regulation of integrin turnover by outside-in activation

MHC class II deprivation impairs CD4 T cell motility and responsiveness to antigen-bearing dendritic cells in vivo

Integrins in immunity

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