INTRAFLAGELLAR TRANSPORT - ESBEN LORENTZEN
The eukaryotic cell is highly organized with specific functions and macromolecules distributed to membrane-enclosed compartments also known as organelles. One such organelle, the cilium, is found on almost all cells in the human body where it is responsible for 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 my lab we work on the logistic problem of how to specifically target macromolecules to the cilium. More than 600 proteins are estimated to function in the cilium and all of these proteins are made in the cell body and thus need to be actively recruited to the cilium. 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 a large macromolecular complex that mediates the transport of proteins to the cilium. Our lab aims to shed light on 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 some ciliary pathologies.
The lab recently received the ERC starting grant to investigate structural and regulatory aspects of intraflagellar transport (2012-2017)
Published papers by the lab in 2012 include:
Taschner, M., Vetter M, and Lorentzen, E., PNAS (2012)
The following review gives and up-to-date account of structural studies of ciliary assemblies:
Mizuno, N., Taschner, M., Engle, BD., and Lorentzen, E., Journal of Molecular Biology (2012)