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Dr. Esben Lorentzen

Group Leader
Phone:+49 89 8578 - 3479

MPI of Biochemistry, Am Klopferspitz 18, 82152 Martinsried

www.biochem.mpg.de/lorentzen

Intraflagellar Transport

Research Group "Intraflagellar Transport"

INTRAFLAGELLAR TRANSPORT

The eukaryotic cell is highly organized with specific functions and macromolecules distributed to various compartments. One such compartment is the cilium, a hair-like organelle that is found on the surface of almost all cells in the human body where it functions in motility and sensory reception. An increasing number of genetic diseases and syndromes (collectively known as ciliopathies) have in recent years been mapped to genes encoding ciliary proteins. Understanding how the cilium is made and what goes wrong in ciliopathies is thus of vital importance.

In our lab we work on the logistic problem of how macromolecules are specifically targeted to the cilium, a process required for the formation, maintenance and function of cilia. More than 600 proteins are estimated to reside in the cilium and thus require active transport from their site of translation in the cytosol. This process is known as IntraFlagellar Transport (IFT) and relies on molecular motors as well as on a large protein complex (the IFT complex) that is thought to mediate the contacts between motors and ciliary cargoes. Mutations in core IFT proteins commonly lead to the absence of cilia and are lethal at the embryonic stage in knockout mice. It is currently not known how the approximately twenty IFT proteins assemble into large macromolecular complexes that mediate IFT. Our lab aims at elucidating this process by reconstituting and determining molecular structures of IFT complexes. We hope that this line of research will not only expand our knowledge concerning cilium assembly and maintenance but also help to understand the molecular basis for ciliary pathologies.

NEWS

The lab recently received a 20 miilion DKR grant from the Novo Nordisk Foundation and will be moving to the department of molecular biology and genetics at the University of Aarhus http://www.novonordiskfonden.dk/en/content/new-grant-type-brings-two-talented-researchers-denmark

Published papers by the lab in 2015-2016 include:

Taschner M., Weber K., Mourão A., Vetter M, Awasthi M., Stiegler M., Bhogaraju S, Lorentzen E., (2016) Intraflagellar transport proteins 172, 80, 57, 54, 38, and 20 form a stable tubulin-binding IFT-B2 complex. EMBO J. pii: e201593164.

Steger M., Tonelli F., Ito G., Davies P., Trost M., Vetter M., Wachter S., Lorentzen E., Duddy G., Wilson S., Baptista MA., Fiske BK., Fell MJ., Morrow JA., Reith AD., Alessi DR., Mann M., (2016) Phosphoproteomics reveals that Parkinson's disease kinase LRRK2 regulates a subset of Rab GTPases. Elife. pii: e12813. doi: 10.7554/eLife.12813

Vetter, M., Stehle, R., Basquin, C., and Lorentzen, E., (2015) Structure of Rab11-FIP3-Rabin8 reveals simultaneous binding of FIP3 and Rabin8 effectors to activated Rab11, Nat Struct Mol Biol, 22(9):695-702

The following review gives and up-to-date account of IFT complx architecture and cargo interactions:

Bhogaraju SEngel BDLorentzen E., (2013) Intraflagellar transport complex structure and cargo interactions, CILIA 2(1):10. doi: 10.1186/2046-2530-2-10

 
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