The mechanism of signal transduction by the GPI anchored Prod 1 protein

摘要: Salamanders such as the red spotted newt Notophthalamus viridescens and the axolotl Ambystoma mexicanum regenerate a number of anatomical structures following injury. Prod1 is believed to guide patterning processes operating during limb regeneration, however molecular mechanism through which it operates unclear. Being glycosylphosphatidylinositol (GPI) anchored, Prod1 does not make direct contact with cytoplasm, raising questions to how functions in transfer information across cell membrane. The transmembrane epidermal growth factor receptor was shown associate with Prod1, initiating MAPK signalling and resulting induction matrix metalloprotease 9 expression (MMP9). MMP9 known be rapidly upregulated hours amputation wound epithelium, a structure essential for regeneration formed by migration cells across surface plane. Patches skin explanted into culture were used model this process. A sheet cells expressing MMP9 seen migrate out from patches, be sensitive MMP inhibitors. Further this, upregulation to occur dermis explanted layer be instructive limb. The relationship Prod1s structure its inducing function was investigated through creation series point mutants, shown that amino acids located on α-helix protein this function. Axolotl lacks GPI anchor, despite requirement of newt anchorage order induce either newt or cells, fully functional either species. There some indication that may confer this ability Prod1.