Extracellular chloride signals collagen IV network assembly during basement membrane formation.
J Cell Biol
; 213(4): 479-94, 2016 05 23.
Article
in En
| MEDLINE
| ID: mdl-27216258
ABSTRACT
Basement membranes are defining features of the cellular microenvironment; however, little is known regarding their assembly outside cells. We report that extracellular Cl(-) ions signal the assembly of collagen IV networks outside cells by triggering a conformational switch within collagen IV noncollagenous 1 (NC1) domains. Depletion of Cl(-) in cell culture perturbed collagen IV networks, disrupted matrix architecture, and repositioned basement membrane proteins. Phylogenetic evidence indicates this conformational switch is a fundamental mechanism of collagen IV network assembly throughout Metazoa. Using recombinant triple helical protomers, we prove that NC1 domains direct both protomer and network assembly and show in Drosophila that NC1 architecture is critical for incorporation into basement membranes. These discoveries provide an atomic-level understanding of the dynamic interactions between extracellular Cl(-) and collagen IV assembly outside cells, a critical step in the assembly and organization of basement membranes that enable tissue architecture and function. Moreover, this provides a mechanistic framework for understanding the molecular pathobiology of NC1 domains.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Basement Membrane
/
Chlorides
/
Collagen Type IV
Limits:
Animals
/
Humans
Language:
En
Journal:
J Cell Biol
Year:
2016
Type:
Article