Molecular characterization of Rab8 membrane tubules as neuromodulatory and neuroprotective membrane trafficking organelles

• Applicant: Dr. Kai Murk
• Subject Area: Molecular Biology and Physiology of Neurons and Glial Cells ; Cell Biology
• Term: since 2025
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 562104233

The function of neurons in the central nervous system (CNS) relies on close interactions with astrocytes. These glia cells modulate most cerebral functions, such as controlling homeostasis, providing metabolic support, and modulating synaptic processes. During disease and injury, reactive astrocytes efficiently protect neurons, notably by sealing them off from neurotoxic factors, restraining aggressive immune cells, and providing trophic support. Key mechanisms enabling these astrocyte functions are complex membrane trafficking processes, which are poorly understood. We recently identified Rab8+ tubular endosomes that reactive astrocytes require for damage containment and neuroprotection during traumatic injury. Our unpublished observations indicate that these Rab8+ tubular endosomes contact autophagosomes and, thereby, regulate autophagy-based protein degradation and/or secretion. In the proposed project, we will use a combinational approach of ‘loss function’, biochemical, and live imaging experiments to dissect in astrocytes the functions of Rab8a and Rab8b in autophagy-dependent degradation and membrane trafficking. Furthermore, we will take advantage of live and fixed imaging assays to study how neurons respond in culture and in vivo when we manipulate Rab8a/8b-dependent membrane trafficking in astrocytes under healthy and injury conditions. In summary, the proposed project will generate a substantially better understanding of astrocyte membrane trafficking pathways, which are integral for CNS functions in healthy and disease.

• DFG Programme: Research Grants