PDZ proteins bind, cluster, and synaptically colocalize with Eph receptors and their ephrin ligands.
Localizing cell surface receptors to specific subcellular positions can be critical for their proper functioning, as most notably demonstrated at neuronal synapses. PDZ proteins apparently play critical roles in such protein localizations. Receptor tyrosine kinases have not been previously shown to interact with PDZ proteins in vertebrates. We report that Eph receptors and their membrane-linked ligands all contain PDZ recognition motifs and can bind and be clustered by PDZ proteins. In addition, we find that Eph receptors and ligands colocalize with PDZ proteins at synapses. Thus, PDZ proteins may play critical roles in localizing vertebrate receptor tyrosine kinases and/or their ligands and may be particularly important for Eph function in guidance or patterning or at the synapse.
Torres
Richard
R
Regeneron Pharmaceuticals, Tarrytown, New York 10591-6707, USA.
Firestein
Bonnie L
BL
Dong
Hualing
H
Staudinger
Jeff
J
Olson
Eric N
EN
Huganir
Richard L
RL
Bredt
David S
DS
Gale
Nicholas W
NW
Yancopoulos
George D
GD
D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000502:physiology* / Q000648:ultrastructure; D003001:Cloning, Molecular; D016384:Consensus Sequence; D036388:Ephrin-B2; D007150:Immunohistochemistry; D008024:Ligands; D008565:Membrane Proteins / Q000032:analysis / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D012441:Saccharomyces cerevisiae; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013569:Synapses / Q000502:physiology; D014162:Transfection
D036388:Ephrin-B2; D008024:Ligands; D008565:Membrane Proteins; D011993:Recombinant Fusion Proteins; D020794:Receptor Protein-Tyrosine Kinases