title: Basement membrane deposition of nidogen 1 but not nidogen 2 requires the nidogen binding module of the laminin gamma1 chain.
abstract: The nidogen-laminin interaction is proposed to play a key role in basement membrane (BM) assembly. However, though there are similarities, the phenotypes in mice lacking nidogen 1 and 2 (nidogen double null) differ to those of mice lacking the nidogen binding module (γ1III4) of the laminin γ1 chain. This indicates different cell- and tissue-specific functions for nidogens and their interaction with laminin and poses the question of whether the phenotypes in nidogen double null mice are caused by the loss of the laminin-nidogen interaction or rather by other unknown nidogen functions. To investigate this, we analyzed BMs, in particular those in the skin of mice lacking the nidogen binding module. In contrast to nidogen double null mice, all skin BMs in γ1III4-deficient mice appeared normal. Furthermore, although nidogen 1 deposition was strongly reduced, nidogen 2 appeared unchanged. Mice with additional deletion of the laminin γ3 chain, which contains a γ1-like nidogen binding module, showed a further reduction of nidogen 1 in the dermoepidermal BM; however, this again did not affect nidogen 2. This demonstrates that in vivo only nidogen 1 deposition is critically dependent on the nidogen binding modules of the laminin γ1 and γ3 chains, whereas nidogen 2 is independently recruited either by binding to an alternative site on laminin or to other BM proteins.
authors.affiliation: Department of Dermatology, University Hospital of Cologne, 50937 Cologne, Germany.
authors.forename: Sharada
authors.initials: S
authors.lastname: Mokkapati
authors.forename: Anja
authors.initials: A
authors.lastname: Fleger-Weckmann
authors.forename: Manuela
authors.initials: M
authors.lastname: Bechtel
authors.forename: Manuel
authors.initials: M
authors.lastname: Koch
authors.forename: Dirk
authors.initials: D
authors.lastname: Breitkreutz
authors.forename: Ulrike
authors.initials: U
authors.lastname: Mayer
authors.forename: Neil
authors.initials: N
authors.lastname: Smyth
authors.forename: Roswitha
authors.initials: R
authors.lastname: Nischt
mesh_terms: D000818:Animals; D001485:Basement Membrane / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D017353:Gene Deletion; D007797:Laminin / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout
chemical_list: D002135:Calcium-Binding Proteins; D015815:Cell Adhesion Molecules; D007797:Laminin; D008562:Membrane Glycoproteins; C112846:Nid2 protein, mouse; C089141:laminin gamma 1; C029967:nidogen