Collagen IV Exploits a Cl- Step Gradient for Scaffold Assembly
Collagen molecules are crucial extracellular players in animal tissue development and in functions ranging from ultrafiltration to organism locomotion. Among the 28 types of collagen found in human, type IV collagen stands out as a primordial type found i
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Collagen IV Exploits a Cl- Step Gradient for Scaffold Assembly Sergey V. Ivanov, Ryan Bauer, Elena N. Pokidysheva, and Sergei P. Boudko Abstract
Collagen molecules are crucial extracellular players in animal tissue development and in functions ranging from ultrafiltration to organism locomotion. Among the 28 types of collagen found in human, type IV collagen stands out as a primordial type found in all species of the animal kingdom. Collagen IV forms smart scaffolds for basement membranes, sheet-like acellular structures that isolate, coordinate, and direct cells during morphogenesis. Collagen IV is also involved in multiple functions in developed tissues. As part of the basement membrane, collagen IV scaffolds provide mechanical strength, spatially tether extracellular macromolecules and directly signal to cells via receptor binding sites. Proper assembly and structure of the scaffolds are critical S. V. Ivanov, R. Bauer, and E. N. Pokidysheva Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN, USA S. P. Boudko (*) Department of Medicine, Division of Nephrology and Hypertension, Vanderbilt University Medical Center, Nashville, TN, USA Vanderbilt Center for Matrix Biology, Vanderbilt University Medical Center, Nashville, TN, USA Department of Biochemistry, Vanderbilt University, Nashville, TN, USA e-mail: [email protected]
for development and function of multiple types of basement membranes. Within last 5 years it was established that Cl concentration is a key factor for initiating collagen IV scaffold assembly. The biological role of Cl in multiple physiological processes and detailed mechanisms for its signaling and structural impacts are well established. Cl gradients are generated across the plasma and intracellular organelle membranes. As collagen IV molecules are secreted outside the cell, they experience a switch from low to high Cl concentration. This transition works as a trigger for collagen IV scaffold assembly. Within the scaffold, collagen IV remains to be a Cl sensor as its structural integrity continues to depend on Cl concentration. Here, we review recent findings and set future directions for studies on the role of Cl in type IV collagen assembly, function, and disease. Keywords
Basement membrane · Cl · Collagen IV · Extracellular matrix · Kinetics · NC1 domain · Protein assembly
Abbreviations NC1 7S
non-collagenous domain 1 of collagen IV 7 Svedberg, the dodecameric region of collagen IV
S. V. Ivanov et al.
ECM BM GBM LBM NC1sc PEG
extracellular matrix basement membrane glomerular BM lens capsule BM single polypeptide chain NC1 trimer polyethylene glycol
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Introduction
Basement membranes (BMs) are evolutionary ancient and highly conserved sheet-like structures of extracellular matrix (ECM) that coordinate cells, direct their polarization, and play a formative role in shaping tissues (Morrissey and Sherwood 2015). In a
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