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

Nature Communications
Jaeho YoonIra O Daar

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.

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Citations

Apr 17, 2019·Journal of Cell Science·Adam Shellard, Roberto Mayor
Jul 28, 2020·Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences·Adam Shellard, Roberto Mayor
Mar 27, 2019·Cell Communication and Signaling : CCS·Sheng-An SuMeixiang Xiang
May 30, 2020·Development·David A Cruz Walma, Kenneth M Yamada
Jan 15, 2021·The Journal of Cell Biology·Gopinath KulasekaranPeter S McPherson
Jan 20, 2021·Development·Jaeho YoonIra O Daar
Jan 12, 2021·Frontiers in Cell and Developmental Biology·Victoria Rozés-SalvadorCecilia Conde
Dec 20, 2020·Cellular and Molecular Life Sciences : CMLS·Enrico CastroflorioPeter L Oliver
Jan 6, 2021·Genes·Tung-Lin LeeChen-Chi Wu

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Datasets Mentioned

BETA
BC128694

Methods Mentioned

BETA
Co-IP
Co-immunoprecipitation assay
immunoprecipitation
confocal microscopy
Co-IPs
PCR
genotyping

Software Mentioned

Prism5
CRISPRdirect
Matlab

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