Institute of Biochemistry, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Institute of Anatomy, Charité - Universitätsmedizin Berlin, Berlin, Germany.
Nat Commun. 2021 Mar 5;12(1):1490. doi: 10.1038/s41467-021-21662-x.
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 β1-integrin. Our work shows that DBN-mediated membrane trafficking in astrocytes is an important neuroprotective mechanism following traumatic brain injury in mice.
哺乳动物的大脑缺乏显著的神经元再生能力，因此特别脆弱。为了保护大脑免受损伤和疾病的影响，星形胶质细胞通过星形胶质细胞增生和瘢痕形成进行损伤控制至关重要。在这里，我们表明，小鼠的脑损伤会立即引发星形胶质细胞中肌动蛋白结合蛋白 Drebrin（DBN）的上调，这对于瘢痕形成和维持星形胶质细胞反应性是必不可少的。反过来，DBN 的缺失会导致脑损伤后星形胶质细胞瘢痕形成缺陷和神经退行性病变过度。在细胞水平上，我们表明 DBN 将肌动蛋白动态平衡从 ARP2/3 依赖性阵列切换到微管兼容的支架，从而促进 RAB8 阳性膜小管的形成。这种损伤特异性的 RAB8 膜隔室充当涉及星形胶质细胞增生和粘附介质（如β1 整合素）的表面蛋白运输的枢纽。我们的工作表明，DBN 介导的星形胶质细胞中的膜运输是小鼠创伤性脑损伤后的一种重要神经保护机制。
