TBC1d24-ephrinB2 interaction regulates contact inhibition of locomotion in neural crest cell migration.

Yoon, Jaeho; Hwang, Yoo-Seok; Lee, Moonsup; Sun, Jian; Cho, Hee Jun; Knapik, Laura; Daar, Ira O.

Although Eph-ephrin signalling has been implicated in the migration of cranial neural crest (CNC) cells, it is still unclear how ephrinB transduces signals regulating this event. We provide evidence that TBC1d24, a putative Rab35-GTPase activating protein (Rab35 GAP), complexes with ephrinB2 via the scaffold Dishevelled (Dsh) and mediates a signal affecting contact inhibition of locomotion (CIL) in CNC cells. Moreover, we found that, in migrating CNC, the interaction between ephrinB2 and TBC1d24 negatively regulates E-cadherin recycling in these cells via Rab35. Upon engagement of the cognate Eph receptor, ephrinB2 is tyrosine phosphorylated, which disrupts the ephrinB2/Dsh/TBC1d24 complex. The dissolution of this complex leads to increasing E-cadherin levels at the plasma membrane, resulting in loss of CIL and disrupted CNC migration. Our results indicate that TBC1d24 is a critical player in ephrinB2 control of CNC cell migration via CIL. Group migration of cranial neural crest cells depends upon Eph-ephrin signalling. Here, the authors show that TBC1d24 complexes with ephrinB2 via Dishevelled to induce contact inhibition of locomotion by reducing membrane E-cadherin. Eph receptor binding dissolves this complex and disrupts migration.

Nature Communications, 2018, Vol 9, Issue 1, p1

2041-1723

Academic Journal

10.1038/s41467-018-05924-9