Importance of a syndapin-mediated interconnection of cytoskeleton and membrane trafficking for neuronal structure, function and plasticity

• Applicant: Professorin Dr. Britta Qualmann
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells
• Term: from 2008 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 65984042

Postsynaptic plasticity mechanisms are considered to be the structural basis of learning and memory. To meet the requirements of growth, adaptation and plasticity of the brain, dynamic adaptations reflected in changes in number, morphology and reorganization of synaptic contacts in response to diverse stimuli are indispensable. At the molecular level, these processes in postsynaptic specializations are characterized by the modulation of the plasma membrane levels of AMPA-type glutamate receptors and by dynamics of the actin cytoskeleton. A coordination of structural reorganizations including formation, maturation and plastic restructuring of synapses with a modulation of the activatable AMPA-receptor proportion through regulation of receptor endocytosis and recycling by molecular links of these processes provides an attractive unifying mechanism for activity-dependent synapse modification. Our previous analyses in non-neuronal cells have demonstrated that syndapins play an essential role in actin cytoskeletal dynamics, receptor-mediated endocytosis and endosomal recycling of membrane receptors and furthermore ensure functional interconnections between these different cellular functions. The morphological and functional characterization of the inducible knockout mice of the mainly neuronal syndapin I isoform that we have established shall unravel the role of this coordinator protein in the structural organization and dynamics of postsynaptic morphology as well as in receptor membrane trafficking processes. Analyses in the course of this project at the whole animal level, in functional brain sections and in primary cell culture systems shall reveal how syndapin I-mediated interconnections of actin dynamics, specialized cytomatrix components of the postsynaptic density, receptor-mediated endocytosis and endosomal receptor recycling overtake coordinative functions that are crucial for the formation, maturation, preservation, function and plastic modulation of postsynaptic nerve endings and thus underlie neuronal plasticity.

• DFG Programme: Research Grants