Coexpressed EphA receptors and ephrin-A ligands mediate opposing actions on growth cone navigation from distinct membrane domains.
Contact-dependent signaling between membrane-linked ligands and receptors such as the ephrins and Eph receptor tyrosine kinases controls a wide range of developmental and pathological processes. Paradoxically, many cell types coexpress both ligands and receptors, raising the question of how specific signaling readouts are achieved under these conditions. Here, we studied the signaling activities exerted by coexpressed EphA receptors and GPI-linked ephrin-A ligands in spinal motor neuron growth cones. We demonstrate that coexpressed Eph and ephrin proteins segregate laterally into distinct membrane domains from which they signal opposing effects on the growth cone: EphAs direct growth cone collapse/repulsion and ephrin-As signal motor axon growth/attraction. This subcellular arrangement of Eph-ephrin proteins enables axons to discriminate between cis- versus trans-configurations of ligand/receptor proteins, thereby allowing the utilization of both Ephs and ephrins as functional guidance receptors within the same neuronal growth cone.
Marquardt
Till
T
Gene Expression Laboratory, The Salk Institute for Biological Studies, 10010 North Torrey Pines Road, La Jolla, California 92037, USA.
Shirasaki
Ryuichi
R
Ghosh
Sourav
S
Andrews
Shane E
SE
Carter
Nigel
N
Hunter
Tony
T
Pfaff
Samuel L
SL
D000818:Animals; D001369:Axons / Q000378:metabolism*; D019556:COS Cells; D002451:Cell Compartmentation / Q000502:physiology*; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D036342:Ephrins / Q000378:metabolism*; D020439:Growth Cones / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism; D009046:Motor Neurons / Q000166:cytology / Q000378:metabolism; D036081:Receptors, Eph Family / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D036342:Ephrins; D036081:Receptors, Eph Family