Repulsion or adhesion: receptors make the call

University of Wisconsin–Madison, Madison, Wisconsin, United States
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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    • "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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    • "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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