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

Authors

• J Yoon
• YS Hwang
• M Lee
• J Sun
• L Knapik
• IO Daar

Abstract

Although Eph-ephrin signaling has been implicated in the migration of cranial neural crest (CNC) cells, it is still unclear how ephrinB transduces signals affecting 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, ephrinB2 interacts with TBC1d24, which in turn 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 inhibition of CNC migration. Our results indicate that TBC1d24 is a critical player in ephrinB2 control of CNC cell migration via CIL.

Scientific Focus Area: Developmental Biology

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