Human WIPI β‐propeller function in autophagy and neurodegeneration

Human WIPI β-propellers fulfill important functions in autophagy as phosphatidylinositol 3-phosphate effectors. The underlying scaffolding function is physiologically essential as WIPI mutations have dramatic effects on human health, particularly causing neurodegenerative diseases. The connection between WIPI mutations (A), the process of autophagy (B) and the neurodegenerative diseases (C) caused by WIPI mutations is given special attention in this review. The four human WIPI β-propellers, WIPI1 through WIPI4, belong to the ancient PROPPIN family and fulfill scaffold functions in the control of autophagy. In this context, WIPI β-propellers function as PI3P effectors during autophagosome formation and loss of WIPI function negatively impacts autophagy and contributes to neurodegeneration. Of particular interest are mutations inWDR45, the human gene that encodes WIPI4. SporadicWDR45 mutations are the cause of a rare human neurodegenerative disease called BPAN, hallmarked by high brain iron accumulation. Here we discuss the current understanding of the functions of human WIPI β-propellers and address unanswered questions with a particular focus on the role of WIPI4 in autophagy and BPAN.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: In a Nutshell Source Type: research