A novel fibronectin binding site required for fibronectin fibril growth during matrix assembly

Jan L. Sechler, Hongwei Rao, Anne Marie Cumiskey, Irbert Vega-Colón, Michael S. Smith, Takatoshi Murata, Jean E. Schwarzbauer

Research output: Contribution to journalArticlepeer-review

94 Scopus citations

Abstract

Fibronectin (FN) assembly into a fibrillar extracellular matrix is a stepwise process requiring participation from multiple FN domains. Fibril formation is regulated in part by segments within the first seven type III repeats (III1-7). To define the specific function(s) of this region, recombinant FNs (recFNs) containing an overlapping set of deletions were tested for the ability to assemble into fibrils. Surprisingly, recFN lacking type III repeat III1 (FNΔIII1), which contains a cryptic FN binding site and has been suggested to be essential for fibril assembly, formed a matrix identical in all respects to a native FN matrix. Similarly, displacement of the cell binding domain in repeats III9-10 to a position close to the NH2-terminal assembly domain, as well as a large deletion spanning repeats III4-7, had no effect on assembly. In contrast, two deletions that included repeat III2, ΔIII1-2, and ΔIII2-5, caused significant reductions in fibril elongation, although binding of FN to the cell surface and initiation of assembly still proceeded. Using individual repeats in binding assays, we show that III2 but not III1 contains an FN binding site. Thus, these results pinpoint repeat III2 as an important module for FN-FN interactions during fibril growth.

Original languageEnglish (US)
Pages (from-to)1081-1088
Number of pages8
JournalJournal of Cell Biology
Volume154
Issue number5
DOIs
StatePublished - Sep 3 2001

All Science Journal Classification (ASJC) codes

  • Cell Biology

Keywords

  • Fibronectin
  • Matrix assembly
  • RGD sequence
  • Self-association
  • Type III repeats

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