Tom Rapoport (Harvard, HHMI) 1: Organelle Biosynthesis and Protein Sorting

https://www.ibiology.org/cell-biology/protein-sorting

Eukaryotic cells have many different membrane-bound organelles with distinct functions and characteristic shapes. How does this happen? Dr. Tom Rapoport explains the important role of protein sorting in determining organelle shape and function.

In his first talk, Dr. Tom Rapoport explains that eukaryotic cells contain many membrane-bound organelles each of which has a characteristic shape and distinctive functions that are carried out by specific proteins. Most proteins are made in the cytosol but must move to different cellular destinations. Protein sorting is determined by signal sequences on the proteins that act as “zip codes”. Many proteins sort first to the endoplasmic reticulum (ER) before moving to other intracellular organelles or the plasma membrane. Rapoport explains that as a protein is translated, its signal sequence causes the nascent protein to insert into the Sec61 channel on the ER membrane. The polypeptide segment following the signal sequence will then be translocated across the membrane. Solving the structure of Sec61 channel allowed Rapoport’s lab to understand how proteins, which are typically hydrophilic, can be transported across a lipid membrane. It also helped them determine how Sec 61 differentiates between secreted proteins which need to be released into the ER lumen and transmembrane proteins which need to be anchored in the ER membrane. This improved knowledge of protein sorting helps us to better understand how organelles are formed and how they function.

The ER is a vast network that includes different domains with different functions. The rough ER consists of sheets with associated ribosomes and is involved in protein translation. The smooth ER consists of tubules and is important for lipid synthesis and Ca2+ transport. In his second talk, Rapoport explains how his lab identified proteins needed to generate and maintain a tubular ER network. They found two families of proteins that are required to form the high membrane curvature of tubules, and membrane-bound GTPases that fuse the tubules together into a network. The tubule-shaping proteins are also important in forming the edges of the ER sheets. In mammalian cells, however, another set of proteins is required to act as spacers between the membrane sheets. Using ultra-thin section electron microscopy, Rapoport’s lab, in collaboration with others, was able to show that stacked ER sheets are held together by helicoidal membrane connections forming a “parking-garage” like structure.

Speaker Biography:
Dr. Tom Rapoport has been a Professor of Cell Biology at Harvard Medical School since 1995 and a Howard Hughes Medical Institute Investigator since 1997. Prior to joining Harvard, Rapoport was a Professor at the Institute for Molecular Biology in East Berlin, which later became the Max-Delbrück Institute for Molecular Medicine. Rapoport received his PhD from Humboldt University of Berlin.

Rapoport’s research focuses on the understanding how organelles, in particular the endoplasmic reticulum (ER), derives its characteristic shape and performs its specific functions. He has had a long standing interest in how proteins are translocated across organelle membranes. His pioneering research has been recognized with many awards including the Max-Delbrück Medal in 2005, the Sir Hans Kreb Medal in 2007, and the Schleiden Medal in 2011, among many others. Rapoport is a member of the National Academy of Sciences, USA and the German Academy of Sciences, Leopoldina. He is also a Fellow of the American Association for the Advancement of Science (AAAS).

Learn more about Rapoport’s research here:
http://rapoport.hms.harvard.edu

and here:
https://www.hhmi.org/scientists/tom-rapoport

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