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

Jaeho Yoon, Yoo-Seok Hwang, Moonsup Lee, Jian Sun, Hee Jun Cho, Laura Knapik and Ira O. Daar ()
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Jaeho Yoon: National Cancer Institute
Yoo-Seok Hwang: National Cancer Institute
Moonsup Lee: National Cancer Institute
Jian Sun: National Cancer Institute
Hee Jun Cho: National Cancer Institute
Laura Knapik: National Cancer Institute
Ira O. Daar: National Cancer Institute

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract 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.

Date: 2018
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DOI: 10.1038/s41467-018-05924-9

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