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Anne G Rosenwald

Title

Associate Professor
Co-Director, Major in Biology of Global Health, Adjunct Associate Professor, Lombardi Cancer Center

Department

Department of Biology
Research

Research

Eukaryotic cells have many different membrane-bounded organelles within them – like rooms within a house. Each organelle (room) has a specific function and the biological membranes which form the “walls” have unique compositions in terms of both lipid and protein components. Nevertheless, the different organelles must communicate with each other and do so by exchanging material back and forth. In the face of this membrane traffic, how do the organelles maintain their unique membrane compositions? In other words, what regulates communication between different membrane-bound compartments?

Members of the ADP-ribosylation factor (Arf) family have been implicated in the movement of molecules between the various membrane-bound compartments. Arf family members, like other members of the Ras superfamily of small guanine nucleotide binding proteins, bind two different (but related) molecules - guanosine diphosphate (GDP) and guanosine triphosphate (GTP). The exchange of GTP for GDP induces the protein to switch from an inactive state to an active one; thus members of this protein superfamily act as molecular switches for a variety of different cellular processes. In the case of Arf proteins, activation also induces a change in localization – from floating free to becoming bound to membranes. Thus, activated Arf proteins are in the right place to confer regulation on the movements of organelle components.

Arf proteins are highly conserved throughout eukaryotic evolution. Recently, new members of this family have been identified. These proteins are similar to Arfs but more distantly related and have therefore been named Arf-like or Arl proteins. At present, little is known about the Arl subfamily but recent evidence from my laboratory suggests that they too may play roles in regulation of membrane functions. Presently, we are using an approach that combines biochemistry and genetics by studying the functions of the Arl family members in the yeast, Saccharomyces cerevisiae. Recent evidence suggests that the Arl1 protein, the primary one we study, is not only involved in regulation of membrane function, but also helps control potassium ion levels in cells in a way that is unrelated to its role in membrane traffic. Our aim is to uncover the mechanisms by which Arl1 controls these two disparate processes.