XB-ART-55532Nat Commun January 1, 2018; 9 (1): 3491.
TBC1d24-ephrinB2 interaction regulates contact inhibition of locomotion in neural crest cell migration.
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.
PubMed ID: 30154457
Article link: Nat Commun
Genes referenced: cdh1 dvl2 efnb2 ephb1 ephb2 ephb4 rab35l tbc1d24.1
Morpholinos: cdh1 MO1 dvl2 MO1 efnb2 MO2 ephb4 MO2 tbc1d24.1 MO1
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References [+] :
Abbruzzese, ADAM13 cleavage of cadherin-11 promotes CNC migration independently of the homophilic binding site. 2017, Pubmed, Xenbase