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

www.ibiology.org/cell-biology...
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:
rapoport.hms.harvard.edu
and here:
www.hhmi.org/scientists/tom-r...

[@lastchance8142]

Absolutely amazing. I love how he often says, "it's very simple", when describing a system that incorporates many tens of thousands of molecules performing a choreography of miraculous complexity!

[@Sol-gq1pu]

Thanks so much Dr Rapoport!

[@changyongkang7651]

Thank you for good lecture :)

[@viesturssilins858]

Thank you so much for sharing this! It is wonderfull!

[@merlin5by533]

This iBiology series is Brilliant. The complexity just defies creation-by-accident.

[@merlin5by533]

@Dev Rifter Inanimate stuff, doesn't evolve, and most of the archaea class, over 4 billion years old, are still here, and don't use DNA. They are RNA class users. Nothing is left to evolve.

[@scottnineteen]

The characterisation of the cell ....internally it's a 3D interwoven structure of two different entities the microtubules and the ER tubes. Seems amazing.

[@mistersir3020]

All the details of one eukaryotic cell make up a more complex system than the whole macroscopic biological world combined!

[@chunglee6895]

Amazing human intellect

[@CarterColeisInfamous]

we need to come up with some way to have like "dry" organelles that we can mix all together to create the constituent cell... or like some way to "bootstrap" simple cells into complex cells with a series of viruses or like turn a prokaryote into a eukaryote by printing a nuclus inside of it

[@medicinefuture]

your work is really great, I am fond of your work, I want to know about the molecular mechanics, how molecules move to the target, what makes them move,

[@gaymo69]

i think it is just thermal dynamics no? they will probably sample lots of different positions in space due to diffusion, and be arrested/associate for longer periods of time with their target.

[@medicinefuture]

@@gaymo69 I do not think it is simple as that, I think it is an invisible matrix or lattice, that makes molecules move directed by this invisible matrix, or may a quantum mechanical phenomena take place

[@medicinefuture]

​@Λ I think it is not a space-time signal, it is a nonlocal signal, while generated it does its action remotely and instantaneously like quantum entanglement, and the chemicals we measure are the result from this effect, not the cause

[@timblackburn1593]

@@medicinefuture Wow - so that really turns it all upside down. How do we go about specifying/locating the non-local mechanism? I realise there may be motivational constraints.

[@medicinefuture]

​@@timblackburn1593 I think there is a field of some kind controlling the motion and interactions of molecules. The time we discover the nature of that field, we will be in so different era of science or medicine, I feel we are creeping so slowly now because we depend on describing things and look at how they work not really why they work like that or this. The right way is to think about the unseen forces, and how they affect the scene

[@devinyoung5735]

looks like the signal sequence uses a hairpin to pick the lock of the SecY channel protein

[@LAGoff]

How is the mRNA 'exported' to the ribosome? I mean, how does the tRNA (that which -- I assume -- transports the mRNA) know to go left or right or straight. And how does it execute whatever degree turn it needs to make at its final destination in order to fit its cargo into the slot at the ribosome,?

[@KuziKQwertY]

tRNA doesnt transport mRNA, it transports aminoacids to the rybozome-mRNA complex to build a protein.

[@jameschamberlain6700]

call him tom rapoport cayse he can rapup a report ya know what im sayin

[@o2807]

why cant we build the economy around science and scientisfs? instead of workers or capitalists.

[@Orenotter]

You lost me when you started talking about evolution. Math proves it didn't happen, yet you stand there talking about it s if you were there watching. Sorry, but I can't respect that.

[@truthbebold4009]

Agreed, de-evolution from perfect harmony should be the accepted understanding of our history. Sin destroys.

[@user-tk2jy8xr8b]

Math proves it happened, sorry

[@aldenfriend9625]

God you people are so fucking dumb lmfao