V3: an enigmatic isoform of the proteoglycan versican.

V3 is an isoform of the extracellular matrix (ECM) proteoglycan (PG) versican generated through alternative splicing of the versican gene such that the two major exons coding for sequences in the protein core that support chondroitin sulfate (CS) glycosaminoglycan (GAG) chain attachment are excluded. Thus, versican V3 isoform carries no GAGs. A survey of PubMed reveals only 50 publications specifically on V3 versican, so it is a very understudied member of the versican family, partly because to date there are no antibodies that can distinguish V3 from the CS-carrying isoforms of versican, that is, to facilitate functional and mechanistic studies. However, a number of in vitro and in vivo studies have identified the expression of the V3 transcript during different phases of development and in disease, and selective overexpression of V3 has shown dramatic phenotypic effects in "gain and loss of function" studies in experimental models. Thus, we thought it would be useful and instructive to discuss the discovery, characterization, and the putative biological importance of the enigmatic V3 isoform of versican.