Department of Anatomy, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
Department of Convergence Medicine, School of Medicine, Pusan National University, Yangsan, Republic of Korea.
Front Immunol. 2024 Oct 14;15:1460882. doi: 10.3389/fimmu.2024.1460882. eCollection 2024.
UNC13 family (also known as Munc13) proteins are evolutionarily conserved proteins involved in the rapid and regulated secretion of vesicles, including synaptic vesicles and cytotoxic granules. Fast and regulated secretion at the neuronal and immunological synapses requires multiple steps, from the biogenesis of vesicles to membrane fusion, and a complex array of proteins for each step. Defects at these steps can lead to various genetic disorders. Recent studies have shown multiple roles of UNC13D in the secretion of cytotoxic granules by immune cells. Here, the molecular structure and detailed roles of UNC13D in the biogenesis, tethering, and priming of cytotoxic vesicles and in endoplasmic reticulum are summarized. Moreover, its association with immune diseases, including familial hemophagocytic lymphohistiocytosis type 3, macrophage activation syndrome, juvenile idiopathic arthritis, and autoimmune lymphoproliferative syndrome, is reviewed. Finally, the therapeutic application of CRISPR/Cas9-based gene therapy for genetic diseases is introduced.
UNC13 家族（也称为 Munc13）蛋白是进化上保守的蛋白，参与囊泡的快速和调节性分泌，包括突触囊泡和细胞毒性颗粒。神经元和免疫突触的快速和调节性分泌需要多个步骤，从囊泡的生物发生到膜融合，每个步骤都需要一系列复杂的蛋白。这些步骤的缺陷可导致各种遗传疾病。最近的研究表明 UNC13D 在免疫细胞的细胞毒性颗粒分泌中具有多种作用。本文总结了 UNC13D 在细胞毒性囊泡的生物发生、连接和引发以及内质网中的分子结构和详细作用。此外，还综述了其与免疫疾病的关联，包括家族性噬血细胞性淋巴组织细胞增多症 3 型、巨噬细胞活化综合征、幼年特发性关节炎和自身免疫性淋巴增生综合征。最后，介绍了基于 CRISPR/Cas9 的基因治疗在遗传疾病中的治疗应用。
