Biology subjects

Schiweck, J.

Publications and source records attributed to Schiweck, J..

2 recordsLinked to original sources

bioRxiv2024

Deficiency of actin depolymerizing factors ADF/Cfl1 in microglia decreases motility and impairs memory

Microglia are highly motile cells that play a crucial role in the central nervous system in health and disease. Here we show that actin depolymerizing factors ADF and Cofilin1 (Cfl1) are key factors of microglia integrity and function. We found a profound morphological phenotype in absence of ADF and Cfl1 in microglia. In vivo two-photon imaging of microglia with ADF/Cfl1-KO revealed reduced microglial fine processes motility and impaired microglia migration towards a laser-induced lesion. We found increased accumulation of stabilized F-actin and altered microtubule dynamics in ADF/Cfl1-KO microglia, indicating that ADF/Cfl1 are necessary for microglial cytoskeleton dynamics. Interestingly, microglial ADF/Cfl1-deficiency decreased learning and memory, suggesting that impaired microglial cytoskeleton dynamics affect neuronal functions relevant for cognition. Our results reveal a fundamental role of ADF/Cfl1 in microglia function and underscore the importance of these innate immune cells for higher cognitive functions.

neuroscience↗

bioRxiv2020

Drebrin mediates scar formation and astrocyte reactivity during brain injury by inducing RAB8 tubular endosomes

The brain of mammals lacks a significant ability to regenerate neurons and is thus particularly vulnerable. To protect the brain from injury and disease, damage control by astrocytes through astrogliosis and scar formation is vital. Here, we show that brain injury triggers an ad hoc upregulation of the actin-binding protein Drebrin (DBN) in astrocytes, which is essential for the formation and maintenance of glial scars in vivo. In turn, DBN loss leads to defective glial scar formation and excessive neurodegeneration following mild brain injuries. At the cellular level, DBN switches actin homeostasis from ARP2/3-dependent arrays to microtubule-compatible scaffolds and facilitates the formation of RAB8-positive membrane tubules. This injury-specific RAB8 membrane compartment serves as hub for the trafficking of surface proteins involved in astrogliosis and adhesive responses, such as {beta}1-integrin. Our work identifies DBN as pathology-specific actin regulator, and establishes DBN-dependent membrane trafficking as crucial mechanism in protecting the brain from escalating damage following traumatic injuries.

neuroscience↗