My research group aims to uncover the molecular mechanisms involved in membrane trafficking and recycling in synapses at nanometer resolution. We study of the transport, docking and fusion of secretory vesicles and the sorting of critical synaptic proteins through endosomes. Endosome recycling is important for the maintenance of basic neurotransmission, but it is also highly dysregulated in neurogenerative diseases such as Alzheimer's disease. We aim to understand the causal relation between disease progression and the disruption of the endolysosomal pathway.

Our group also runs the VU campus Electron Microscopy Facility, where we make advanced electron microscopy techniques available for all researchers at the VU campus and beyond. We specialize in cryofixation and quantitative morphometric analysis of ultrastructural elements. By this, we contribute to multiple high impact publications from the center for Neurogenomics and Cognitive Research (CNCR), Cancer Center Amsterdam (CCA) and other institutes based at the VU campus including Amsterdam UMC, location VUmc. More recently, we combine electron microscopy with a wide variety of (super-resolution) fluorescence microscopy techniques to investigate these dynamic processes in living cells as well as observing specific pathological hallmarks in patient brain material.

Specialized techniques: transmission electron microscopy, cryofixation, correlative light electron microscopy (CLEM), electron tomography, super-resolution imaging, live cell imaging

Key publications:

Gowrisankaran S, Houy S, Del Castillo JGP, Steubler V, Gelker M, Kroll J, Pinheiro PS, Schwitters D, Halbsgut N, Pechstein A, van Weering JRT, Maritzen T, Haucke V, Raimundo N, Sørensen JB, Milosevic I.Endophilin-A coordinates priming and fusion of neurosecretory vesicles via intersectin. Nat Commun. 2020 Mar 9;11(1):1266. doi: 10.1038/s41467-020-14993-8.

van Weering JRT, Scheper W. Endolysosome and Autolysosome Dysfunction in Alzheimer's Disease: Where Intracellular and Extracellular Meet. CNS Drugs. 2019 Jun 4. doi: 10.1007/s40263-019-00643-1.

Wiersma V, van Ziel, AM, Vazquez-Sanchez S, Nolle A, Berenjeno-Correa E, Bonaterra-Pastra A, Clavaguera F, Musters RJP, van Weering JRT, Verhage M, Scheper W. Granulovacuolar degeneration bodies are neuron-selective lysosomal structures induced by intracellular tau pathology. Acta Neuropathol. 2019 Aug 27. doi: 10.1007/s00401-019-02046-4.

Persoon CM, Hoogstraaten R, van Weering JRT, Kaeser PS, Toonen RF and Verhage M. The Rab3-RIM pathway is essential for neuropeptide release. Neuron. 2019 Dec 18;104(6):1065-1080.e12. doi: 10.1016/j.neuron.2019.09.015.

Vazquez-Sanchez S, Bobeldijk S, Dekker MP, van Keimpema L, van Weering JRT. VPS35 depletion does not impair presynaptic structure and function. Sci Rep. 2018 Feb 14;8(1):2996. doi: 10.1038/s41598-018-20448-4.

Bugiani M*, Dubey M*, Breur M, Postma NL, Dekker MP, Ter Braak T, Boschert U, Abbink TEM, Mansvelder HD, Min R, van Weering JRT*, van der Knaap MS*. Megalencephalic leukoencephalopathy with cysts: the Glialcam-null mouse model.Ann Clin Transl Neurol. 2017 Jun 6;4(7):450-465.

van Weering JRT, Cullen PJ, Membrane-associated cargo recycling by tubule-based endosomal sorting.Semin Cell Dev Biol. (2014) Jul;31:40-7. doi: 10.1016/j.semcdb.2014.03.015.

Kurps J, Broeke JH, Cijsouw T., Kompatscher A., van Weering JRT*, de Wit H*. Quantitative image analysis tool to study the plasma membrane localization of proteins and cortical actin in neuroendocrine cells. J Neurosci Methods. (2014) 30;236:1-10. doi: 10.1016/j.jneumeth.2014.07.022. * contributed equally

van Weering, JRT, Sessions, RB, Traer, CJ, Kloer DP, Bhatia VK, Stamou D, Hurley, JH and Cullen PJ Molecular basis for SNX-BAR-mediated assembly of distinct endosomal sorting tubules.EMBO J (2012), vol 31(23) pp. 4466-80