RT Journal Article
SR Electronic
T1 Kindlin2 enables EphB/ephrinB bi-directional signaling to support vascular development
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202201800
DO 10.26508/lsa.202201800
VO 6
IS 3
A1 Li, Wenqing
A1 Wen, Lai
A1 Rathod, Bhavisha
A1 Gingras, Anne-Claude
A1 Ley, Klaus
A1 Lee, Ho-Sup
YR 2023
UL https://www.life-science-alliance.org/content/6/3/e202201800.abstract
AB Direct contact between cells expressing either ephrin ligands or Eph receptor tyrosine kinase produces diverse developmental responses. Transmembrane ephrinB ligands play active roles in transducing bi-directional signals downstream of EphB/ephrinB interaction. However, it has not been well understood how ephrinB relays transcellular signals to neighboring cells and what intracellular effectors are involved. Here, we report that kindlin2 can mediate bi-directional ephrinB signaling through binding to a highly conserved NIYY motif in the ephrinB2 cytoplasmic tail. We show this interaction is important for EphB/ephrinB-mediated integrin activation in mammalian cells and for blood vessel morphogenesis during zebrafish development. A mixed two-cell population study revealed that kindlin2 (in ephrinB2-expressing cells) modulates transcellular EphB4 activation by promoting ephrinB2 clustering. This mechanism is also operative for EphB2/ephrinB1, suggesting that kindlin2-mediated regulation is conserved for EphB/ephrinB signaling pathways. Together, these findings show that kindlin2 enables EphB4/ephrinB2 bi-directional signal transmission.