Emerging Groups of C-Type Lectins
Layilin, a ~55-kDa lectin, is a widely expressed integral membrane hyaluronan receptor, originally identified as a binding partner of talin located in membrane ruffles. It is recruited to membrane ruffles in cells induced to migrate in in vitro wounding e
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40
G.S. Gupta
40.1
Layilin Group of C-Type Lectins (Group VIII of CTLDS)
40.1.1 Layilin: A Hyaluronan Receptor Layilin, a ~55-kDa lectin, is a widely expressed integral membrane hyaluronan receptor, originally identified as a binding partner of talin located in membrane ruffles. It is recruited to membrane ruffles in cells induced to migrate in in vitro wounding experiments and in peripheral ruffles in spreading cells. Layilin is a transmembrane C-type lectin (Fig. 40.1) and binds specifically to hyaluronan (HA) but not to other tested glycosaminoglycans and belongs to group VIII of CTLDs. The other member of this group is chondrolectin. Layilin’s ability to bind hyaluronan reveals an interesting parallel between layilin and CD44, because both can bind to cytoskeleton-membrane linker proteins through their cytoplasmic domains and to hyaluronan through their extracellular domains. This parallelism suggests a role for layilin in cell adhesion and motility (Banerji et al. 1999; Bono et al. 2001). There is no sequence homology with known hyaluronan receptors, including CD44, RHAMM (receptor for HA-mediated motility), or LYVE-1 (lymphatic vessel endothelial HA receptor-1). Thus, by binding to HA, layilin may facilitate cell migration by mediating early interactions between spreading cells and the extracellular matrix (ECM). Since, hyaluronan is involved in invasion of a variety of tumor cells and layilin was detected in the human lung cell line A549, layilin might play crucial roles in lymphatic metastasis of lung carcinoma. Suppression of layilin expression by iRNA significantly increased survival of tumor-bearing mice. The suppression of layilin expression might be a promising strategy for treatment of human lung carcinoma (Chen et al. 2008).
40.1.2 Interactions of Layilin The actin cytoskeleton plays a significant role in change of cell shape and motility. Several adaptor proteins, including talin, maintain the cytoskeleton-membrane linkage by binding to integral membrane proteins and to the cytoskeleton. The talin binds to integrins, vinculin, actin and layilin. A ten-amino acid motif in layilin cytoplasmic domain is sufficient for talin binding. Layilin colocalizes with talin in ruffles and binds to talin’s ~50-kDa head domain (amino acids 280–435). This region overlaps a binding site for focal adhesion kinase (Borowsky and Hynes 1998). The other known binding partners of layilin include other members of the talin/band 4.1/ERM (ezrin, radixin, and moesin) family of cytoskeletal-membrane linker molecules. The neurofibromatosis 2 tumor suppressor protein, merlin, is commonly mutated in human benign brain tumors. Merlin and radixin interact with the carboxy-terminal domain of layilin. This 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 et al. 2005; Scoles 2008). The talin F3 domain binds to short sequences in the layilin cyto
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