A Novel Member of the Netrin Family, β-Netrin, Shares Homology with the β Chain of Laminin : Identification, Expression, and Functional Characterization

Abstract

The netrins are a family of laminin-related molecules. Here, we characterize a new member of the family, β-netrin. β-Netrin is homologous to the NH ₂ terminus of laminin chain short arms; it contains a laminin-like domain VI and 3.5 laminin EGF repeats and a netrin C domain. Unlike other netrins, this new netrin is more related to the laminin β chains, thus, its name β-netrin. An initial analysis of the tissue distribution revealed that kidney, heart, ovary, retina, and the olfactory bulb were tissues of high expression. We have expressed the molecule in a eukaryotic cell expression system and made antibodies to the expressed product. Both in situ hybridization and immunohistochemistry were used to describe the cellular source of β-netrin and where β-netrin is deposited. β-Netrin is a basement membrane component; it is present in the basement membranes of the vasculature, kidney, and ovaries. In addition, β-netrin is expressed in a limited set of fiber tracts within the brain, including the lateral olfactory tract and the vomeronasal nerve. Functional studies were performed and show that β-netrin promotes neurite elongation from olfactory bulb explants. Together, these data suggest that β-netrin is important in neural, kidney, and vascular development.