title: Binding of netrin-4 to laminin short arms regulates basement membrane assembly.
abstract: Netrins were first identified as neural guidance molecules, acting through receptors that are members of the DCC and UNC-5 family. All netrins share structural homology to the laminin N-terminal domains and the laminin epidermal growth factor-like domains of laminin short arms. Laminins use these domains to self-assemble into complex networks. Here we demonstrate that netrin-4 is a component of basement membranes and is integrated into the laminin polymer via interactions with the laminin gamma1 andgamma3 short arms. The binding is mediated through the laminin N-terminal domain of netrin-4. In contrast to netrin-4, other members of the netrin family do not bind to these laminin short arms. Moreover, a truncated form of netrin-4 completely inhibits laminin-111 self-assembly in vitro, and full-length netrin-4 can partially disrupt laminin self-interactions. When added to explant cultures, netrin-4 retards salivary gland branching morphogenesis.
authors.affiliation: Center for Biochemistry, University of Cologne, Joseph-Stelzmann-Strasse 52, D-50931 Cologne, Germany.
authors.forename: Fiona I
authors.initials: FI
authors.lastname: Schneiders
authors.forename: Barbara
authors.initials: B
authors.lastname: Maertens
authors.forename: Kerstin
authors.initials: K
authors.lastname: Böse
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
authors.forename: William J
authors.initials: WJ
authors.lastname: Brunken
authors.forename: Mats
authors.initials: M
authors.lastname: Paulsson
authors.forename: Neil
authors.initials: N
authors.lastname: Smyth
authors.forename: Manuel
authors.initials: M
authors.lastname: Koch
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000166:cytology*; D002478:Cells, Cultured; D007797:Laminin / Q000378:metabolism*; D051379:Mice; D009024:Morphogenesis; D009154:Mutation; D009414:Nerve Growth Factors / Q000235:genetics / Q000378:metabolism*; D000075385:Netrins; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012469:Salivary Glands / Q000166:cytology
chemical_list: C504220:Lamc3 protein, mouse; D007797:Laminin; D009414:Nerve Growth Factors; D000075385:Netrins; C416214:Ntn4 protein, mouse; C089141:laminin gamma 1