Saitoh Shinji
Department of Pediatrics and Neonatology, Graduate School of Medical Sciences, Nagoya City University, Kawasumi 1, Mizuho-cho, Mizuho-ku, Nagoya 467-8601, Japan.
Cells. 2022 Jan 3;11(1):148. doi: 10.3390/cells11010148.
The quality and quantity of membrane proteins are precisely and dynamically maintained through an endosomal recycling process. This endosomal recycling is executed by two protein complexes: retromer and recently identified retriever. Defects in the function of retromer or retriever cause dysregulation of many membrane proteins and result in several human disorders, including neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease. Recently, neurodevelopmental disorders caused by pathogenic variants in genes associated with retriever were identified. This review focuses on the two recycling complexes and discuss their biological and developmental roles and the consequences of defects in endosomal recycling, especially in the nervous system. We also discuss future perspectives of a possible relationship of the dysfunction of retromer and retriever with neurodevelopmental disorders.
膜蛋白的质量和数量通过内体循环过程得以精确且动态地维持。这种内体循环由两种蛋白质复合物执行:逆转录复合物和最近发现的回收复合物。逆转录复合物或回收复合物功能的缺陷会导致许多膜蛋白失调,并引发多种人类疾病,包括阿尔茨海默病和帕金森病等神经退行性疾病。最近,已确定由与回收复合物相关基因的致病变异引起的神经发育障碍。本综述聚焦于这两种循环复合物,讨论它们在生物学和发育中的作用以及内体循环缺陷的后果,特别是在神经系统中的后果。我们还讨论了逆转录复合物和回收复合物功能障碍与神经发育障碍可能关系的未来前景。