Layilin, a cell surface hyaluronan receptor, interacts with merlin and radixin.
Layilin is a widely expressed integral membrane hyaluronan receptor, originally identified as a binding partner of talin located in membrane ruffles. We have identified merlin, the neurofibromatosis type 2 tumor suppressor protein and radixin, as other interactors with the carboxy-terminal domain of layilin. We show that the carboxy-terminal domain of layilin is capable of binding to the amino-terminal domain of radixin. An interdomain interaction between the amino- and the carboxy-terminal domains of radixin inhibits its ability to bind to layilin. In the presence of acidic phospholipids, the interdomain interaction of radixin is inhibited and layilin can bind to full-length radixin. In contrast, layilin binds both full-length and amino-terminal merlin-GST fusion proteins without a requirement for phospholipids. Furthermore, layilin antibody can immunoprecipitate merlin, confirming association in vivo between these two proteins, which also display similar subcellular localizations in ruffling membranes. No interaction was observed between layilin and ezrin or layilin and moesin. These findings expand the known binding partners of layilin to include other members of the talin/band 4.1/ERM (ezrin, radixin, and moesin) family of cytoskeletal-membrane linker molecules. This in turn suggests that layilin may mediate signals from extracellular matrix to the cell cytoskeleton via interaction with different intracellular binding partners and thereby be involved in the modulation of cortical structures in the cell.
Bono
Petri
P
Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Cordero
Etchell
E
Johnson
Kristen
K
Borowsky
Mark
M
Ramesh
Vijaya
V
Jacks
Tyler
T
Hynes
Richard O
RO
D016475:3T3 Cells; D000818:Animals; D001798:Blood Proteins / Q000187:drug effects / Q000378:metabolism*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000187:drug effects / Q000378:metabolism*; D005982:Glutathione Transferase / Q000378:metabolism; D018960:Hyaluronan Receptors / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D025581:Neurofibromin 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D010743:Phospholipids / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016608:Talin / Q000378:metabolism / Q000494:pharmacology
D001798:Blood Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D018960:Hyaluronan Receptors; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D025581:Neurofibromin 2; D010743:Phospholipids; D011993:Recombinant Fusion Proteins; D016608:Talin; C115279:layilin protein, mouse; C071776:radixin; D005982:Glutathione Transferase