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


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.

SUBMITTER: Yoon J 

PROVIDER: S-EPMC6113226 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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

Yoon Jaeho J   Hwang Yoo-Seok YS   Lee Moonsup M   Sun Jian J   Cho Hee Jun HJ   Knapik Laura L   Daar Ira O IO  

Nature communications 20180828 1


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  ...[more]

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