Willem Annaert
Laboratory for Membrane Trafficking
VIB Department of Molecular and Developmental Genetics, K.U.Leuven
PhD: University of Antwerp, Belgium
Postdoc: Yale University & HHMI, USA, '94-'96;
Center for Human Genetics, KULeuven, ’97-2001;
VIB Group leader since 2001
VIB Adjunct Department Director since 2007
Full Professor, KULeuven since 2008
e-mail: wim.annaert@cme.vib-kuleuven.be
phone: +32 16 33 05 20
address: Gasthuisberg, Herestraat 49, O&N1 9th floor, Rm. 9.696, BE-3000 Leuven BELGIUM
Current team members
Group leader: Willem Annaert
Postdoctoral scientists: Tim Raemaekers, Ragna Sannerud, Dragana Spasic, Milos Spasic, Cary Esselens
Ph.D. Students: Ellen Reynders, Deepak Balaji Thimiri Govinda Raj, Katrijn Coen, Aleks Peric, Ekaterina Ivanova, Applonia Josephine Rose, Arun Kumar Tharkeshwar
Technical Staff: Christine Michiels, Ilse Declerck, Veerle Baert, Wendy Vermeire, Huiqi Lu, Christine Nys, Genia De Brauwer
Science, relevant to NERF
How do dysfunctions in endomembrane transport contribute to the pathology of Alzheimer’s disease?
Dysfunction in the neuronal endo-lysosomal system is recognized as one of the earliest pathological features in sporadic Alzheimer’s disease. This system plays an increasing role in the generation of amyloid β peptides –the major culprit in Alzheimer’s disease– from its precursor APP during the process of regulated intramembrane proteolysis. We hypothesize that the differential localization of various γ-secretase complexes and substrates in nanodomains at the cell surface and endosomes is part of the mechanism defining specificity in APP processing. Also more generally, we want to identify at the molecular level how presenilins affects protein turnover during endosomal trafficking in neurons. Here we believe that presenilin is selectively interfering with internalization routes in cells and neurons. This idea emerged from our seminal findings that presenilin deficiency results in the selective accumulation of the cell adhesion molecule ICAM-5 in yet unidentified degradative organelles. Using the cell adhesion molecule ICAM-5 as a read-out we have identified this affected route and now explore in detail the role presenilin plays herein.
In support of these projects, we make substantial efforts to improve the resolution of our technologies. Superresolution confocal microscopy (PALM) enables us to resolve at single protein level the nanodomain association of APP and γ-secretase components; the development of superparamagnetic nanoparticles opens novel avenues for subcellular proteomics and biomarker identifications.
Interactions with NERF
Our cell biological studies have fostered several interests from the site of IMEC with respect to programs on cell-based biosensors (i) and nanoparticles (ii).
(i) High signal-to-noise recordings from electrogenic cells depend on very tight contacts between the sensor and the cell membrane. We have used the features of ICAM-5 in cell adhesion and neuronal phagocytosis to grow primary neurons on multielectrode arrays. Selfassembled monolayers functionalized with selected peptides applied on microfabricated Au needles create a tight seal beneficial for the signal coupling from the cell membrane into a transducer.
(ii) We have optimized superparamagnetic nanoparticles (∅10nm) (SMNPs) that target the cell surface allowing us to combine one-step plasmamembrane isolations with mass spec analysis (proteomics, lipidomics, glycomics). A second generation of SMNPs is being developed coated with biomolecules (toxins, ligands, antibodies) for neuronal endosomal targeting. Magnetic isolation followed by ‘organellar proteomics’ will generate proteome inventories of ligand-specific axonal and dendritic endosomal carriers. SMNPs may provide a powerful tool to identify for instance novel biomarkers in Alzheimer’s disease but also in cancer and stem cell research. They could also be further developed as ‘smart delivery’ vehicles for DNA, RNA or drugs into specific cell and neuron populations.
Hence, while these ongoing collaborations already bridge these disciplines in the two partner institutions, we are convinced that these areas of investigation can be further strengthened and explored by new researchers at NERF.
Selected publications
- Esselens, C., Oorschot, V., Baert, V., Raemaekers, T., Spittaels, K., Serneels, L., Zheng, H., De Strooper, B., Klumperman, J., and Annaert, W. Presenilin 1 mediates the turnover of telencephalin in hippocampal neurons via an autophagic degradative pathway. J. Cell Biol. 166(7); 1041-54, 2004.
- Spasic, D., Raemaekers, T.*, Dillen, K.*, Declerck, I., Baert, V., Serneels, L., Füllekrug, J., Annaert, W. Rer1p competes with APH-1 for binding to Nicastrin and regulates g-secretase complex assembly in the early secretory pathway. J. Cell Biol. 176(5), 629-640, 2007.
- Van Meerbergen, B.*, Raemaekers, T.*, Winters, K., Braeken, D., Bartic, C., Spira, M., Engelborghs, Y., Annaert, W. and Borghs, G. Improving neuronal adhesion on chip using a phagocytosis-like event. J. Exp. Nanoscience, Vol. 2, 1-2, 101-114, 2007.
- Jans,K., Van Meerbergen, B., Reekmans, G., Bonroy, K., Annaert, W., Maes, G., Engelborghs, Y., Borghs, G. Bartic, C. Chemical and biological characterization of Thiol SAMs for neuronal cell attachment. Langmuir, 25(8): 4564-70, 2009.
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