Department of Inflammation and Immunity, Learner Research Institute, Cleveland Clinic Foundation, Cleveland, OH 44195, USA.
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA; Department of Physiology and Biophysics, Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA.
Trends Cell Biol. 2023 Jan;33(1):48-59. doi: 10.1016/j.tcb.2022.06.006. Epub 2022 Jul 9.
Gasdermin B (GSDMB) belongs to a family of structurally related proteins [(i.e., gasdermins (GSDMs)]. It distinguishes itself from other members by the lack of autoinhibition but clear bioactivity of its full-length form, its preference to bind to phosphatidylinositol phosphates and sulfatides, and the ability to promote both lytic and nonlytic cellular functions. It is the only gasdermin that lacks a mouse ortholog, making in vivo mechanistic studies challenging to perform. GSDMB is abundantly expressed in epithelial cells lining organs that directly interface with the external environment, such as the gastrointestinal tract, with emerging evidence supporting its role in enteric infections, inflammatory bowel disease (IBD), and colorectal cancer. This review discusses the unique features of GSDMB among other gasdermin family members and controversies surrounding GSDMB-dependent mammalian inflammatory cell death (i.e., pyroptosis), including recent discoveries revealing both lytic and nonlytic functions of epithelial-derived GSDMB, particularly during gut health and disease.
Gasdermin B (GSDMB) 属于结构相关蛋白家族 [(即，gasdermins (GSDMs)]。它与其他成员的区别在于全长形式缺乏自动抑制作用，但具有明确的生物活性，偏爱与磷脂酰肌醇磷酸和硫酸脑苷脂结合，以及促进裂解和非裂解细胞功能的能力。它是唯一缺乏小鼠同源物的 gasdermin，使得体内机制研究难以进行。GSDMB 在与外部环境直接接触的器官上皮细胞中大量表达，例如胃肠道，有新的证据支持其在肠感染、炎症性肠病 (IBD) 和结直肠癌中的作用。这篇综述讨论了 GSDMB 在其他 gasdermin 家族成员中的独特特征以及围绕 GSDMB 依赖性哺乳动物炎症细胞死亡（即细胞焦亡）的争议，包括最近的发现揭示了上皮衍生的 GSDMB 的裂解和非裂解功能，特别是在肠道健康和疾病期间。
