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Getting into shape

Tom Rapoport, speaker of the second MDC lecture, dedicated his career to the endoplasmic reticulum (ER). The ER is the cell compartment, or organelle, which is the entry site into the secretory pathway. There, secretory proteins and constituents of the secretory pathway are produced, folded, packaged and addressed for prompt delivery to their final destinations. The ER also takes care of quality control and waste sorting and has many other functions, which scientists are just beginning to understand.

 

MDC alumnus Tom Rapoport left the MDC in 1995 for the Harvard Medical School. Picture: Rapoport/HHMI

The morphology of this busy organelle is intriguing. It is a structure of interlaced tubules surrounding the nucleus and extending into, in some cells even seemingly filling, the cytoplasm. It is a continuous system, but consisting of a series of morphologically distinct domains, with each domain having a specialized function.

The basic question

Tom Rapoport’s research is about finding the blueprint for this architecture. In his talk titled “How do organelles get into shape?”, Tom gave an account of his lab’s successful journey of addressing this question. The talk was a showcase of biochemistry – clear reductionist approach utilizing a plethora of cutting edge methodologies while asking the next logical question – this is inspiration for all basic research scientists and the secret to Tom’s success.

 

Anett Köhler, postdoc of the Sommer lab: “Today I saw my favorite organelle in a new light.” Picture: L. Bengtsson/MDC

For Anett Köhler, a postdoc in Thomas Sommer lab, the talk was an eye-opener. “I’m working on ERAD, the ER garbage disposal system, and have never thought about the ER’s shape. Today I saw my favorite organelle in a new light.”

Homecoming

“It was great hearing the old colleague in his usual high quality”, commented Franz Noll and Ernst-Georg Krause, former group leaders at the MDC. Old colleague, because Tom Rapoport was himself a group leader at the Akademie der Wissenschaften der DDR, Zentralinstitut für Molekularbiologie and the MDC before moving his lab to Harvard University, School of Medicine in 1995. The MDC Lecture was in a way his 20-year anniversary of leaving the MDC. “The campus changed so much, it’s non-recognizable”, said Tom, “but I’m still recognizing some faces, that’s nice. We’re aging as a cohort…”

 

MDC alumni Franz Noll and Ernst-Georg Krause: “It’s a pleasure to hear an old colleague in his usual high quality.” Picture: Luiza Bengtsson/MDC

New old traditions

The aging cohort was by far not the only audience of Tom’s talk. The MDC community seems to have accepted the new lecture series and filled the Axon 1 completely. This is not a common sight, given the many lectures and talks offered at the MDC daily. “Back in the days, when we started the Berlin Lecture on Molecular Medicine”, told Tom, “we had a 20-people committee deciding on speakers and inviting to the talks. This was our trick of ensuring enough attendance”.

Berlin Lecture on Molecular Medicine is the precursor of the MDC Lecture and was called into life in 1992 by Tom Rapoport and Detlev Ganten, the founding director of the MDC. The very first speaker was Günter Blobel, the 1999 Nobel Prize winner. The second speaker, Sydney Brenner, won the Nobel Prize in 2002. Other high profile, internationally recognized scientists followed. The committee had a good nose for groundbreaking scientists, with maybe one exception: Tom’s suggestion to invite Alfred Gilman as the third speaker was voted down. A pity, as it would have made a series - later that year Alfred Gilman was awarded the Noble Prize.

The Berlin Lecture left some big shoes to fill for its new edition, the MDC Lecture. This time the organization is slightly different: the 20-person committee got extended to all of the MDC and there are four MDC Lectures per year. This allows each research area (cardio, neuro, cancer and systems biology) to decide on one candidate per year. Walter Birchmeier coordinates and aids the effort, assisted by Nuria Cerda-Esteban from the scientific directorate.

Bottom line

The Berlin Lecture needed organizational overhaul and a fresh start. The new concept is working, and who knows – maybe the next Nobel Prize awardees will be Fred Alt (1st MDC Lecture) and Tom Rapoport?

As for the getting into shape for the ER, Tom and his research team have uncovered some of the blueprint. In essence – the protein families Atlastins, Lunapark and Reticulons cooperate to impose a certain curvature on the edges of the tubuli membranes and forcing them into forming three-way junctions. These three-way-junctions are the basis for the network structure of the ER. What appears as sheets on electron microscopy images, are the ER membranes stacked upon each other. Tom’s lab used 3D-image reconstruction approaches and found out, that these stacks are in fact interconnected ‘platforms’. Together they create a shape resembling a parking garage. A protein travelling the ER simply needs to always take a turn in the same direction to traverse the ER from top to the bottom. The advantage of this design? Energy- and space-efficiency! No packaging, no secretion costs, no interruptions, the proteins can travel between the ER stacks without leaving their familiar environment. Additionally, this design provides the cell with means to fit a lot of ER-membranes into its cramped premises.

 

Thomas Sommer, interim director of the MDC with Tom Rapoport: "I wouldn’t be here if it wasn’t for Tom; he recruited me.” Picture: Luiza Bengtsson/MDC

Tom Rapoport summarized, looking at the audience: “Organelle shape is a complicated scientific question, with still many unknowns. Hopefully you guys can help solving some of them”. To the question “any other wishes or comments for the MDC community?” he answered enthusiastically “oh, that’s an easy one: way to go!”