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Tiam-Rac signaling mediates trans-endocytosis of ephrin receptor EphB2 and is
important for cell repulsion
#MMPMID27597758
Gaitanos TN
; Koerner J
; Klein R
J Cell Biol
2016[Sep]; 214
(6
): 735-52
PMID27597758
show ga
Ephrin receptors interact with membrane-bound ephrin ligands to regulate
contact-mediated attraction or repulsion between opposing cells, thereby
influencing tissue morphogenesis. Cell repulsion requires bidirectional
trans-endocytosis of clustered Eph-ephrin complexes at cell interfaces, but the
mechanisms underlying this process are poorly understood. Here, we identified an
actin-regulating pathway allowing ephrinB(+) cells to trans-endocytose EphB
receptors from opposing cells. Live imaging revealed Rac-dependent F-actin
enrichment at sites of EphB2 internalization, but not during vesicle trafficking.
Systematic depletion of Rho family GTPases and their regulatory proteins
identified the Rac subfamily and the Rac-specific guanine nucleotide exchange
factor Tiam2 as key components of EphB2 trans-endocytosis, a pathway previously
implicated in Eph forward signaling, in which ephrins act as in trans ligands of
Eph receptors. However, unlike in Eph signaling, this pathway is not required for
uptake of soluble ligands in ephrinB(+) cells. We also show that this pathway is
required for EphB2-stimulated contact repulsion. These results support the
existence of a conserved pathway for EphB trans-endocytosis that removes the
physical tether between cells, thereby enabling cell repulsion.
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