Neurons are highly specialized cells with complex cytoarchitecture, as their dendrites and axons extend hundreds of micrometers from the soma and sustain thousands of synaptic connections. Maintaining these connections requires tight spatial and temporal control of synaptic protein turnover. Lysosomes, which function as degradative organelles and as the terminal compartment of both autophagic and endocytic pathways, play a central role in this process.
In this seminar, Katarzyna M. Grochowska, PhD will present recent research showing that dendritic lysosomal membranes are heterogeneous and include a distinct subset of lysosomes capable of exocytosis. Upon activation of N-methyl-D-aspartate receptors (NMDARs), these lysosomes directly bind the NMDAR scaffold Dlg3/SAP102 and subsequently fuse with the plasma membrane. Their cargo includes chaperone-mediated autophagy substrates, among them disease-relevant, aggregation-prone proteins such as transactive response DNA-binding protein 43 (TDP-43), belonging to the metastable, supersaturated protein subset.
Katarzyna M. Grochowska, PhD will also discuss how lysosomal fusion with the plasma membrane leads to the extracellular release of proteases, facilitating matrix remodeling and promoting dendritic spine growth. Together, these findings suggest a mechanistic link between activity-driven lysosomal exocytosis, the removal of chaperone-mediated autophagy substrates, and the structural plasticity of dendritic spine synapses.
About the speaker
Katarzyna M. Grochowska, PhD is a synapse biologist at the Center for Molecular Neurobiology (ZMNH), University Hospital Hamburg-Eppendorf, Germany, where she leads the research group Synaptic Proteostasis (SynPro). Her research focuses on the molecular mechanisms underlying synaptic protein homeostasis and their relevance to age-related neurodegenerative diseases.
She completed her doctorate at the Leibniz Institute for Neurobiology under the supervision of Prof. Eckart D. Gundelfinger and Dr Michael R. Kreutz. Her doctoral research explored amyloid-β and synapse-to-nucleus signalling in neurodegenerative diseases. Prior to this, she obtained a Master’s degree in Biotechnology from the Warsaw University of Life Sciences, with thesis work carried out at the Nencki Institute of Experimental Biology in the group led by Prof. Kaczmarek under the supervision of Dr Izabela Figiel.
Dr Grochowska also completed a Bachelor’s degree in Biotechnology jointly pursued at the Warsaw University of Life Sciences and the University of Ghent. During this time, she undertook research stays at institutions in Poland, Belgium, and France. Her interdisciplinary and international training has shaped a research profile focused on understanding how synaptic proteostasis contributes to neuronal function and dysfunction.
