Amassin (white) sticks sea urchin immune cells together.

The olfactomedin (OLF) protein domain appears in a strange assortment of places: its namesake, olfactomedin, is found in the mucous covering the bullfrog olfactory neuroepithelium, while mutations in the OLF domain of human myocilin/TIGR protein are associated with a form of familial glaucoma, and the OLF-containing protein noelin appears to be involved in neural crest formation in vertebrates. But what does this conserved domain do? On page 597, Hillier and Vacquier identify another OLF-containing protein, show that it mediates a novel form of intercellular adhesion, and describe a simple but powerful model system for future work in this area.

The authors set out to understand how cells in the coelom of a sea urchin clot in response to an injury. In contrast to vertebrate or arthropod blood clotting, sea urchin clotting involves rapid aggregation of phagocytic immune cells. A factor that promotes clotting was isolated from the coelomic fluid, partially sequenced, and cloned. The plasma protein, called amassin, forms disulfide bonds to aggregate into large complexes. About half of the amassin sequence is an OLF domain, and structural predictions show a strong resemblance to OLF domains from other species.

Since amassin, calcium, and plasma-free cells from the coelom are the only components required for sea urchin clotting, the system is a simple model for studying OLF-mediated intercellular adhesion. The authors speculate that clot-like cell adhesion may be a general function of OLF domains. In familial glaucoma, for example, mutant myocilin/TIGR is thought to mediate a cellular clustering process that decreases aqueous outflow from the eye, increasing intraocular pressure.

Amassin appears to require a cell surface receptor for clot formation, but the receptor and the mechanism that triggers clotting remain unknown. Hillier and Vacquier are now trying to determine the crystal structure of the amassin OLF domain and understand its regulation. ▪