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J Cell Biol. 2016 May 23;213(4):479-94. doi: 10.1083/jcb.201510065.

Extracellular chloride signals collagen IV network assembly during basement membrane formation.

Author information

1
Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN 37232 Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232 Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN 37232.
2
Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232 Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN 37232.
3
Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232 Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN 37232 Center for Structural Biology, Vanderbilt University Medical Center, Nashville, TN 37232.
4
Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232 Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN 37232 Aspirnaut Program, Vanderbilt University Medical Center, Nashville, TN 37232.
5
Aspirnaut Program, Vanderbilt University Medical Center, Nashville, TN 37232 Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232.
6
School of Life Sciences, Tsinghua University, Beijing 100084, China.
7
Department of Biology, Vanderbilt University Medical Center, Nashville, TN 37232 Aspirnaut Program, Vanderbilt University Medical Center, Nashville, TN 37232.
8
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN 37232.
9
Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232.
10
Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, TN 37232.
11
Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232 Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN 37232 Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232 Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232.
12
Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232 Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN 37232 Department of Cancer Biology, Vanderbilt University Medical Center, Nashville, TN 37232 Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232.
13
Department of Biochemistry, Vanderbilt University Medical Center, Nashville, TN 37232 Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN 37232 Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN 37232 Aspirnaut Program, Vanderbilt University Medical Center, Nashville, TN 37232 Department of Pathology, Microbiology, and Immunology, Vanderbilt University Medical Center, Nashville, TN 37232 Department of Cell and Developmental Biology, Vanderbilt University Medical Center, Nashville, TN 37232 Vanderbilt Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN 37232 Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232 billy.hudson@vanderbilt.edu.

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.

PMID:
27216258
PMCID:
PMC4878091
DOI:
10.1083/jcb.201510065
[Indexed for MEDLINE]
Free PMC Article

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