Tom Rapoport is a Professor of Cell Biology at Harvard Medical School (since January, 1995) and a Howard Hughes Medical Institute Investigator (since July, 1997). He received his Ph.D. degree from Humboldt University, Berlin (East Germany), and his "Habilitation" from the same institution. Before assuming his current position, he was Professor of Cell Biology at the Academy of Sciences of East Germany and later at the Max Delbrück Center for Molecular Medicine. He is an author on more than 200 publications and has received a number of awards.
Tom Rapoport received his Ph.D. for work in enzymology. Together with Reinhart Heinrich, he developed the theory that is now called Metabolic Control Analysis (MCA). At the same time, he worked on the molecular cloning of the cDNA for carp insulin. This brought him into the field of protein translocation which has occupied him ever since. Major discoveries include the reconstitution of co- and post-translational translocation pathways with purified components, the identification of Sec61/SecY complex as the component forming a protein-conducting channel, elucidation of the mechanism by which the signal sequence is recognized, and the identification of a passive partitioning mechanism for the interpretation of membrane proteins. After his move to the U.S., he has worked in several additional areas including molecular motors, DNA transport across membranes, uptake of cholera toxin into cells, mRNA transport, chaperones, and others.
Currently, the Rapoport laboratory is interested in three major projects: One project concerns the translocation of proteins across membranes. They have identified a protein-conducting channel and determined its X-ray structure. A variety of biochemical techniques are being used to understand how polypeptides are moved through the channel. A second project addresses the mechanism by which misfolded proteins of the endoplasmic reticulum (ER) are transported back into the cytosol and degraded by the proteasome (ERAD). Finally, the lab is interested in the question of how the morphology of the ER is generated.
How the endoplasmic reticulum gets into shape
How is the characteristic shape of a membrane-bound organelle achieved? They have addressed the mechanism by which the morphology of the endoplasmic reticulum (ER) is generated. ER tubules are shaped by two families of integral membrane proteins, the reticulons and DP1/Yop1p, which are necessary and sufficient for tubule formation. These proteins may use hydrophobic insertion and scaffolding mechanisms to shape lipid bilayers into tubules. The interconnection of ER tubules in mammalian cells requires the atlastins (ATLs), membrane-bound GTPases of the dynamin family, which promotes the homotypic fusion of ER membranes. Crystal structures of the cytosolic domain of ATL and biochemical experiments have given important insight into the fusion mechanism. Fusion depends on a GTP-hydrolysis induced conformational change in the cytosolic domain. The transmembrane segments contribute to fusion by mediating the oligomerization of ATL molecules prior to fusion, and the following cytoplasmic tail facilitates fusion by interacting with and perturbing the lipid bilayer. A GTPase in yeast and plant, called Sey1p in S.cerevisiae, may have an analogous function to ATL. Their results also suggest that the reticulons and DP1/Yop1p are major determinants of peripheral ER sheets by stabilizing the high membrane curvature of sheet edges. In higher organisms, sheets can be further stabilized by sheet-promoting proteins.
For more information, click here.