Importance of the Nature of Substratum: Discovery of GRASP
Cell-substratum adhesion plays a crucial part in the cascade of events that control cellular growth or turn on and consummate a differentiation program. Adhesion to a selected substratum is a sine qua non requirement for reprograming mature OLGs in culture. We found that plating OLGs on a polylysine surface in DMEM plus 20% horse serum reproduced their morphology and biology seen in situ. We also found that not all batches of horse serum were equally effective. This led to the idea that there must be an active component in horse serum. Indeed, purification of horse serum yielded a heparin-binding glycine-rich glycoprotein – GRASP – with a native molecular mass of Mr X 10-3 = 120-140, of which 24-27% is contributed by carbohydrate that when used as substratum allowed the growth of OLGs in a synthetic medium [11]. We conjecture that GRASP acts as a surrogate for a neuronal signal. The identification of GRASP as a signal transducer generated new and exciting questions to be addressed. One, what transcription factors are activated by GRASP? Are they the same as those that in vivo direct the initial differentiation of OLG progenitors toward a myelinogenic phenotype? Two, is there a neuronal ortholog of GRASP? And, if so, does it bind to the same receptor on the surface of OLGs?