[CITATION][C] Alternative splicing of fibronectin—many different proteins but few different functions

C Ffrench-Constant - Experimental cell research, 1995 - Elsevier
Experimental cell research, 1995Elsevier
Fibronectin (FN) represents perhaps the most extensively studied extracellular matrix
glycoprotein and provides an excellent example for the study of cell–extracellular matrix
interactions. Fibronectin shows a widespread pattern of expression in development and
repair [l], and the observation that a transgenic mouse lacking fibronectin dies during
embryonic development [2] confirms that this expression is essential for normal
development. Cell surface receptors of the integrin family (a 561, a 461, a3/31, av 61, arv (3 …
Fibronectin (FN) represents perhaps the most extensively studied extracellular matrix glycoprotein and provides an excellent example for the study of cell–extracellular matrix interactions. Fibronectin shows a widespread pattern of expression in development and repair [l], and the observation that a transgenic mouse lacking fibronectin dies during embryonic development [2] confirms that this expression is essential for normal development. Cell surface receptors of the integrin family (a 561, a 461, a3/31, av 61, arv (3, avf6, and a IIb/33;[3–10]) as well as cell-surface proteoglycans|| 11, 12] have been characterized. In the case of the integrins, recognition sites within fibronectin have been mapped to specific sequences within fibronectin [4, 13, 14]. More recently, work on the three-dimensional structure of fibronectin has defined the basic structure of the type Ill repeats that form the central core of the molecule [15]. In addition, they have clarified the stereochemistry of one of the recognition sequences, the RGD sequence lying within the type III repeat (III-10), that is recognized by a 5/31 15]. The significant recent advances from studies such as these should pave the way for the design of drugs to mimic or inhibit cell matrix interactions involved in normal repair or blood clot for-nation. ln one area, however, the progress of recent research has been less satisfactory. Fibronectin is encoded by a single gene whose pre-mRNA can be alternatively spliced in three different regions. The extent of splicing was characterized some years ago and has been summarized in the comprehensive review of fibronectin by Hynes [1]. However, we still have a poor understanding of the function of the different alternatively spliced forms of FN and, as a consequence, an incomplete understanding of the significance of the alternative splicing. This review will focus on this aspect of FN, with the dual aims being to summarize current data on the
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