BBB seminar: Anne Simonsen

Anne Simonsen
Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo

Autophagy is a catabolic mechanism that allows recycling of cytoplasmic organelles and macromolecules through their sequestration into double-membrane vesicles (autophagosomes) which fuse with lysosomes, leading to degradation of the sequestered cargo. Long considered a non-selective process, induced in response to cellular starvation, autophagy is now emerging as a highly selective quality control mechanism whose basal levels are important to allow cells to rapidly eliminate superfluous or damaged organelles, as well as unwanted structures as invading pathogens. Recently, our understanding of the hierarchy of autophagy-related proteins has increased significantly, but the membrane remodeling and trafficking events involved in autophagy are still poorly understood.

My lab is interested in the interplay between lipids and lipid-binding proteins in the regulation and execution of autophagy. I will present some of our recent findings showing how membrane input from recycling endosomes to forming autophagosomes is oppositely regulated by the lipid-binding PX domain proteins SNX18 and HS1BP3 [1, 2]. I will also discuss how the phosphatidylinositol 3-phosphate (PtdIns3P)-binding protein ALFY facilitates selective degradation of protein aggregates by autophagy [3-6].

References:

1.  Knævelsrud, H., et al., Membrane remodeling by the PX-BAR protein SNX18 promotes autophagosome formation. J Cell Biol, 2013. 202:331-49.

2.  Holland, P., et al., HS1BP3 negatively regulates autophagy by modulation of phosphatidic acid levels. Nat Commun, 2016. 7:13889.

3.  Simonsen, A., et al., Alfy, a novel FYVE-domain-containing protein associated with protein granules and autophagic membranes. J Cell Sci., 2004. 117:4239-51.

4.  Filimonenko, M., et al., The selective macroautophagic degradation of aggregated proteins requires the PI3P-binding protein Alfy. Mol Cell, 2010. 38:265-79.

5.  Clausen, T.H., et al., p62/SQSTM1 and ALFY interact to facilitate the formation of p62 bodies/ALIS and their degradation by autophagy. Autophagy, 2010. 6:330-44.

6.  Lystad, A.H., et al., Structural determinants in GABARAP required for the selective binding and recruitment of ALFY to LC3B-positive structures. EMBO Rep, 2014. 15:557-65.

Chairperson: Martha Chekenya Enger <martha.enger@uib.no>, Department of Biomedicine