A novel member of the netrin family, beta-netrin, shares homology with the beta chain of laminin: identification, expression, and functional characterization.
The netrins are a family of laminin-related molecules. Here, we characterize a new member of the family, beta-netrin. beta-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 beta chains, thus, its name beta-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 beta-netrin and where beta-netrin is deposited. beta-Netrin is a basement membrane component; it is present in the basement membranes of the vasculature, kidney, and ovaries. In addition, beta-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 beta-netrin promotes neurite elongation from olfactory bulb explants. Together, these data suggest that beta-netrin is important in neural, kidney, and vascular development.
Koch
M
M
Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts 02129, USA.
Murrell
J R
JR
Hunter
D D
DD
Olson
P F
PF
Jin
W
W
Keene
D R
DR
Brunken
W J
WJ
Burgeson
R E
RE
D000595:Amino Acid Sequence; D000818:Animals; D001485:Basement Membrane / Q000737:chemistry; D005260:Female; D005836:Genitalia, Female / Q000737:chemistry; D006801:Humans; D066298:In Vitro Techniques; D007668:Kidney / Q000737:chemistry; D007797:Laminin; D008565:Membrane Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification* / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification* / Q000494:pharmacology; D000075385:Netrins; D016501:Neurites; D009830:Olfactory Bulb / Q000737:chemistry / Q000187:drug effects*; D051381:Rats; D011994:Recombinant Proteins / Q000276:immunology / Q000302:isolation & purification; D017386:Sequence Homology, Amino Acid; D014018:Tissue Distribution
D007797:Laminin; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000075385:Netrins; D011994:Recombinant Proteins; C415837:beta-netrin