Drebrin controls scar formation and astrocyte reactivity upon traumatic brain injury by regulating membrane trafficking

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 in mice triggers an immediate upregulation of the actin-binding protein Drebrin (DBN) in astrocytes, which is essential for scar formation and maintenance of astrocyte reactivity. In turn, DBN loss leads to defective astrocyte scar formation and excessive neurodegeneration following brain injuries. At the cellular level, we show that DBN switches actin homeostasis from ARP2/3-dependent arrays to microtubule-compatible scaffolds, facilitating 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 adhesion mediators, such as beta 1-integrin. Our work shows that DBN-mediated membrane trafficking in astrocytes is an important neuroprotective mechanism following traumatic brain injury in mice. Reactive astrocytes control tissue damage following traumatic brain injury. Here the authors show that Drebrin (DBN) regulates scar formation and astrocyte reactivity in mice. Astrocytic DBN plays its neuroprotective role through the mediation of membrane trafficking.

Automated summary

The study reveals that brain injury in mice leads to an upregulation of DBN protein in astrocytes, which is crucial for scar formation and maintenance of astrocyte reactivity. DBN-mediated membrane trafficking serves as an important neuroprotective mechanism following traumatic brain injury in mice.