Layilin, a novel integral membrane protein, is a hyaluronan receptor

The actin cytoskeleton plays a significant role in changes of cell shape an d motility, and interactions between the actin filaments and the cell membr ane are crucial for a variety of cellular processes. Several adaptor protei ns, including talin, maintain the cytoskeleton-membrane linkage by binding to integral membrane proteins and to the cytoskeleton. Layilin, a recently characterized transmembrane protein with homology to C-type lectins, is a m embrane-binding site for talin in peripheral ruffles of spreading cells. To facilitate studies of layilin's function, we have generated a layilin-Fc f usion protein comprising the extracellular part of layilin joined to human immunoglobulin G heavy chain and used this chimera to identify layilin liga nds. Here, we demonstrate that layilin-Fc fusion protein binds to hyalurona n immobilized to Sepharose. Microtiter plate-binding assays, coprecipitatio n experiments, and staining of sections predigested with different glycosam inoglycan-degrading enzymes and cell adhesion assays all revealed that layi lin binds specifically to hyaluronan but not to other tested glycosaminogly cans. Layilin's ability to bind hyaluronan, a ubiquitous extracellular matr ix component, reveals an interesting parallel between layilin and CD44, bec ause both can bind to cytoskeleton-membrane linker proteins through their c ytoplasmic domains and to hyaluronan through their extracellular domains. T his parallelism suggests a role for layilin in cell adhesion and motility.