Project description in Norwegian - January 2002
Hormones, growth factors, cytokines and many drugs determine cell growth and survival by stimulating receptors on the cell surface. Dysregulation of receptor signalling is associated with cancer. In our research group we are interested in the interplay between receptor signalling and endocytic membrane traffic. We have been studying the function of the small GTPase Rab5 in endocytic membrane fusion, and we have identified several effector molecules that interact with the GTP-bound form of Rab5. One of these effectors is the early endosomal autoantigen EEA1, which, in addition to two Rab5 binding domains, contains a novel zinc binding domain, termed the FYVE finger. We have found that the FYVE finger is involved in the membrane binding of EEA1 via interaction with a specific membrane lipid, phosphatidylinositol 3-phosphate (PI3P). The FYVE finger motif is conserved in a number of other molecules presumed to play a role in membrane traffic or signal transduction, and our working hypothesis is that FYVE finger proteins are recruited to or activated at specific membrane domains through their interactions with PI3P. Our current activities include the identification and functional characterization of novel FYVE finger proteins that function in endocytic or autophagic membrane traffic. For this purpose we study cultured cells by electron and confocal microscopy as well as various biochemical assays. Recently, we have also started to use the fruitfly Drosophila melanogaster as a model organism to study endocytic and autophagic membrane trafficking in a multicellular context. .
Receptor downregulation by endocytosis
Cloning and functional characterization of novel FYVE proteins
The function of phosphatidylinositol 3-phosphate in receptor signalling and membrane trafficking
Autophagy and endocytic trafficking in Drosophila
