Background information
Members of the WIPI subfamily of WD40 repeat proteins, such as WIPI1 (WD repeat domain, phosphoinositide interacting 1), have a 7-bladed propeller structure and contain a conserved motif for interaction with phospholipids. WIPI1 moved through the same set of endosomal membranes as that followed by mannose-6-phosphate receptor (MPR). Consistent with this, WIPI1 was enriched in clathrin-coated vesicles. Overexpression of WIPI1 disrupted the function of the MPR pathway, whereas expression of a double point mutant unable to bind phosphoinositides had no effect. Suppression of WIPI1 by interfering RNA indicated that WIPI1 is required for normal endosomal organization and distribution of IGF2R.