WD repeat domain phosphoinositide-interacting protein 1 (WIPI) is involved in the lysosomal degradation of cytoplasmic components during starvation-induced autophagy. WIPI1 is a seven bladed beta-propeller protein that provides a scaffold for the assembly of multimeric protein complexes (1). During the assembly of the autophagosome WIPI1 interacts with the lipid phosphatidylinositol-3 phosphate (PI3P) and mediates the recruitment of the large multimeric complex of ATG12-ATG5-ATG16 (1). This complex functions as an E3 ligase during the conjugation of phosphatidylethanolamine to LC3. LC3 can then be incorporated into the expanding autophagosomal membrane and recruit substrates that have been targeted for degradation (1). These events were characterized by Polson et al. (2). Using the WIPI1 antibody for western blotting the authors were able to show WIPI1 was required for the lipidation of LC3 (2). Additionally through immunofluorescence with the WIPI1 antibody their study demonstrated the requirement of WIPI1 for the autophagosome maturation process and the formation of LC3-positive autophagosomes (2). Additional studies using WIPI1 antibodies for immunofluorescence have demonstrated WIPI1 localization at both the early phagophore and the autophagosome (3). This localization pattern is induced by starvation and is dependent on PI3P. Detailed examination of WIPI1 was carried out by the Robenek group using freeze-fracture immuno-electron microscopy (4). Detection using WIPI1 antibodies showed WIPI1 localizes to both the inner and outer membranes of the autophagosome upon nutrient starvation (4). In addition to using WIPI1 antibodies as tools to study cell starvation and autophagy, they may also serve important diagnostic functions. Downregulation of WIPI1 has been observed in kidney and pancreatic tumors. The contribution of WIPI1 to cellular transformation in these tumors may be explained by the role of autophagy in cell death and tumor suppression (3). Further research is needed to assess the suitability of using WIPI1 levels for diagnostic purposes.
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