A Novel Member of the Netrin Family, β-Netrin, Shares Homology with the β Chain of Laminin

Author:

Koch Manuel1,Murrell Julie R.2,Hunter Dale D.234,Olson Pamela F.14,Jin William1,Keene Douglas R.5,Brunken William J.16,Burgeson Robert E.1

Affiliation:

1. Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129

2. Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts 02111

3. Department of Anatomy and Cell Biology, Tufts University School of Medicine, Boston, Massachusetts 02111

4. Department of Ophthalmology, Tufts University School of Medicine, Boston, Massachusetts 02111

5. Shriners Hospital for Children, Portland, Oregon 97201

6. Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467

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 NH2 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.

Publisher

Rockefeller University Press

Subject

Cell Biology

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