Tenascin-C: From Discovery to Structure-Function Relationships
Matthias Chiquet
Abstract
INTRODUCTION: HOW TO ISOLATE AN ECM PROTEIN IN 1980 Q7Forty years ago, the tremendous complexity of extracellular matrix (ECM) was still largely anuncharted area, mainly because many of its components could only be solubilized by denaturingagents. Known were just five types of collagens, elastin, a couple of proteoglycans, and a few ECMglycoproteins, among them fibronectin, thrombospondin-1, and laminin-111 (1). The best studiedwas fibronectin (2), which became notorious for promoting specific cell adhesion to collagens. Inparallel, the search for yet undetected large ECM glycoproteins continued. In 1981-82, Carter (3)observed several novel glycoproteins in human fibroblast ECM extracts. Among them, "GP250" wasshown to be distinct from fibronectin but resisted isolation. However, between 1983-85 severalresearch groups independently discovered and characterized a similar ECM glycoprotein that laterbecame known as tenascin-C (see below). Its subunits were comparable in size to fibronectin butinstead of dimers formed large (>106 kDa) disulfide-linked oligomers. In the following paragraphs,the history and context of the individual discoveries of tenascin-C is briefly recounted. I thendescribe how a combination of methods available at the time lead to a detailed structural model oftenascin-C. This was the basis for trying to assign functions to different parts of the molecule. Forreasons outlined below, this turned out to be more difficult than for fibronectin.