Mechanisms and functions of eph and ephrin signalling

Abnormal cerebellar development and axonal decussation due to mutations in AHI1 in Joubert syndrome

“…Several molecules are crucial modulators of commissural fiber crossing, including Slits, Robo and Ephrins 23,24 , but it is not clear how these membrane complexes regulate downstream cytoplasmic signaling partners. AHI1 is as a potential downstream effector of these pathways, as it is essential for commissural crossing in the corticospinal tract and SCPs and encodes a putative cytoplasmic phosphoprotein.…”

Cell–cell signaling via Eph receptors and ephrins

“…The Ephs and ephrins were initially identified as axon guidance molecules mediating neuronal repulsion during CNS development [2][3], but it was soon discovered that they also regulate cell-cell communication in a variety of other tissues and cell types [1,9]. While their best-studied roles outside of the nervous system are those during development of the vascular system, recent studies reveal the importance of Ephs and ephrins in the immune system, bone, stem cells, epithelial cells and in the development and metastasis of many tumors.…”

“…The Ephs and ephrins were first described as modulators of neuronal repulsion [2,3] and only later was discovered that they can also promote cell adhesion [48]. Interestingly, forward signaling seems to be more often repulsive, while reverse signaling via A-class ephrins is mostly attractive/adhesive [48].…”

“…The Eph receptors and their ephrin ligands control a diverse array of cell-cell interactions in the nervous and vascular systems, as well as in specialized epithelia [reviewed in [1][2][3][4]. Upon ephrin binding, the tyrosine kinase domain of the Ephs is activated, initiating "forward" signaling in the receptor-expressing cells.…”

“…Both the Ephs and the ephrins are divided into two subclasses -A and B -based on their affinities for each other and on sequence conservation [6] (http://eph-nomenclature.med.harvard.edu/). In general, the A-subclass Eph receptors (EphA1-EphA9) bind promiscuously to the A-class ephrins (ephrin-A1 -ephrin-A6), while the EphB subclass receptors (EphB1 -EphB6) interact with the B-subclass ephrins (ephrin-B1-ephrin-B3) [1][2][3][4]. Since both Ephs and ephrins are membrane-bound, their interaction occurs only at sites of cell-cell contact (Fig.…”