Repulsion or adhesion: receptors make the call

Department of Zoology, Madison, WI 53706, USA.
Current Opinion in Cell Biology (Impact Factor: 8.47). 11/2006; 18(5):533-40. DOI: 10.1016/
Source: PubMed


Repulsive signaling plays a prominent role in regulating cell-cell interactions and is fundamental to multiple developmental processes. A proper balance between repulsion from and adhesion to other cells or the extracellular matrix is also important. Semaphorin-Plexin and ephrin-Eph ligand-receptor pairs compose two major repulsive signaling systems. Recent advances have elucidated mechanisms by which Semaphorin-Plexin and ephrin-Eph signaling control repulsion versus adhesion. Semaphorins act through a complex signaling pathway to inhibit integrin-mediated adhesion, allowing cell repulsion. Ephrin-Eph interactions can directly mediate cell adhesion and several mechanisms control whether ephrin-Eph binding and signaling induces repulsion or adhesion.

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    • "These domains have been shown to interact with and regulate the activity of a number of small GTPases including direct binding of Rac1, Rnd1, and RhoD to the RBD and less-well defined sequestration of, or GAP activity against, R-Ras and Rap family members (4–6). The end result is often an effect upon cell motility including an extensive crosstalk with integrin-mediated adhesion (7–9). "
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    ABSTRACT: An important role for plexinD1 in thymic development is inferred from studies of germline Plxnd1 knockout (KO) mice where mislocalized CD69(+) thymocytes as well as ectopic thymic subcapsular medullary structures were observed. Given embryonic lethality of the Plxnd1 (-/-) genotype, fetal liver transplantation was employed in these prior analyses. Such embryonic hematopoietic reconstitution may have transferred Plxnd1 KO endothelial and/or epithelial stem cells in addition to Plxnd1 KO lymphoid progenitors, thereby contributing to that phenotype. Here we use Plxnd1 (flox/flox) mice crossed to pLck-Cre, pKeratin14-Cre, or pTek-Cre transgenic animals to create cell-type specific conditional knockout (CKO) lines involving thymocytes (D1ThyCKO), thymic epithelium (D1EpCKO), and thymic endothelium (D1EnCKO), respectively. These CKOs allowed us to directly assess the role of plexinD1 in each lineage. Loss of plexinD1 expression on double positive (DP) thymocytes leads to their aberrant migration and cortical retention after TCR-mediated positive selection. In contrast, ectopic medulla formation is a consequence of loss of plexinD1 expression on endothelial cells, in turn linked to dysregulation of thymic angiogenesis. D1EpCKO thymi manifest neither abnormality. Collectively, our findings underscore the non-redundant roles for plexinD1 on thymocytes and endothelium, including the dynamic nature of medulla formation resulting from crosstalk between these thymic cellular components.
    Frontiers in Immunology 11/2013; 4:392. DOI:10.3389/fimmu.2013.00392
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    • "A distinctive feature of the Eph/ephrin signaling pathway is the ability of both Eph receptors and ephrins to activate signal transduction cascades (respectively called forward and reverse signaling) and its extensive cross-talk with other cell surface receptors, including cadherins and integrins (Arvanitis and Davy, 2008). Although Eph/ephrin signaling is commonly associated with cell repulsion, a number of studies have shown that this signaling cascade might also promote cell-cell and cell-ECM adhesion in certain cellular contexts (Halloran and Wolman, 2006). We are particularly interested in ephrin B1 as it is encoded by an X-linked gene mutation of which causes the human craniofrontonasal syndrome (CFNS) (Twigg et al., 2004; Wieland et al., 2004). "
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    ABSTRACT: Apical neural progenitors are polarized cells for which the apical membrane is the site of cell-cell and cell-extracellular matrix adhesion events that are essential for maintaining the integrity of the developing neuroepithelium. Apical adhesion is important for several aspects of the nervous system development, including morphogenesis and neurogenesis, yet the mechanisms underlying its regulation remain poorly understood. Here, we show that ephrin B1, a cell surface protein that engages in cell signaling upon binding cognate Eph receptors, controls normal morphogenesis of the developing cortex. Efnb1-deficient embryos exhibit morphological alterations of the neuroepithelium that correlate with neural tube closure defects. Using loss-of-function experiments by ex vivo electroporation, we demonstrate that ephrin B1 is required in apical progenitors (APs) to maintain their apical adhesion. Mechanistically, we show that ephrin B1 controls cell-ECM adhesion by promoting apical localization of integrin β1 and we identify ADP-ribosylation factor 6 (Arf6) as an important effector of ephrin B1 reverse signaling in apical adhesion of APs. Our results provide evidence for an important role for ephrin B1 in maintaining the structural integrity of the developing cortex and highlight the importance of tightly controlling apical cell-ECM adhesion for neuroepithelial development.
    Development 04/2013; 140(10). DOI:10.1242/dev.088203 · 6.46 Impact Factor
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    • "Plexins are large transmembrane proteins containing a sema domain and a highly conserved cytoplasmic domain (Tamagnone et al., 1999). They are highly expressed in neurons (Tamagnone et al., 1999; Worzfeld et al., 2004) and mediate axon guidance cues (Halloran and Wolman, 2006). In the developing nervous system, plexins control axon guidance by acting as functional receptors for semaphorins (Kruger et al., 2005; Tamagnone et al., 1999). "
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    ABSTRACT: γδ T cells respond rapidly to keratinocyte damage, providing essential contributions to the skin wound healing process. The molecular interactions regulating their response are unknown. Here, we identify a role for interaction of plexin B2 with the CD100 receptor in epithelial repair. In vitro blocking of plexin B2 or CD100 inhibited γδ T cell activation. Furthermore, CD100 deficiency in vivo resulted in delayed repair of cutaneous wounds due to a disrupted γδ T cell response to keratinocyte damage. Ligation of CD100 in γδ T cells induced cellular rounding via signals through ERK kinase and cofilin. Defects in this rounding process were evident in the absence of CD100-mediated signals, thereby providing a mechanistic explanation for the defective wound healing in CD100-deficient animals. The discovery of immune functions for plexin B2 and CD100 provides insight into the complex cell-cell interactions between epithelial resident γδ T cells and the neighboring cells they support.
    Immunity 08/2012; 37(2):314-25. DOI:10.1016/j.immuni.2012.05.026 · 21.56 Impact Factor
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