About the project
We have previously identified the BDCP ALFY (Autophagy-linked FYVE protein) as being important for selective autophagy of aggregate-prone proteins associated with Huntington’s and Parkinson’s disease. ALFY interacts with the ubiquitin-binding autophagy receptor p62 and links ubiquitinated proteins to the core autophagic machinery through its interactions with ATG5 and PI3P. This project aims to further characterize of the localization and cellular function of all BDCPs. Such knowledge will provide important insight to the pathology in a widespread selection of diseases and may lead to identification of potential diagnostic markers or targets for therapy. An approach combining state-of-the-art genomics, imaging and proteomics technologies with clinically relevant systems and cell biological models, will be used to address these questions.
Outcomes/Recent findings
- ALFY and p62 interacts with the mitochondria proteins NIPSNAP1 and -2 to facilitate mitophagy (PMID: 30982665)
- ALFY is critical for the granulocytic differentiation of AML cells (PMID: 29021535)
- Alfy/WDFY3 is required for establishing neuronal connectivity in the mammalian brain. PMID 27648578
- Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B-positive structures (PMID: 24668264)
- LYST affects lysosome size and quantity, but not trafficking or degradation through autophagy or endocytosis (25216107)
- The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy. (PMID 20417604)
Funding
The University of Oslo, The Research Council of Norway
Collaborations
- Ai Yamamoto, Columbia University, New Work
- Kim Finley, San Diego State University
- Terje Johansen, University of Tromsø