Ji Xiaojie, Chang Bo, Naggert Jürgen K, Nishina Patsy M
The Jackson Laboratory, 04609, Bar Harbor, ME, USA.
Graduate School of Biomedical Sciences and Engineering, University of Maine, 600 Main Street, Orono, USA.
Adv Exp Med Biol. 2016;854:745-50. doi: 10.1007/978-3-319-17121-0_99.
Regulation of vesicle trafficking to lysosomes and lysosome-related organelles (LROs) as well as regulation of the size of these organelles are critical to maintain their functions. Disruption of the lysosomal trafficking regulator (LYST) results in Chediak-Higashi syndrome (CHS), a rare autosomal recessive disorder characterized by oculocutaneous albinism, prolonged bleeding, severe immunodeficiency, recurrent bacterial infection, neurologic dysfunction and hemophagocytic lympohistiocytosis (HLH). The classic diagnostic feature of the syndrome is enlarged LROs in all cell types, including lysosomes, melanosomes, cytolytic granules and platelet dense bodies. The most striking CHS ocular pathology observed is an enlargement of melanosomes in the retinal pigment epithelium (RPE), which leads to aberrant distribution of eye pigmentation, and results in photophobia and decreased visual acuity. Understanding the molecular function of LYST and identification of its interacting partners may provide therapeutic targets for CHS and other diseases associated with the regulation of LRO size and/or vesicle trafficking, such as asthma, urticaria and Leishmania amazonensis infections.
调节囊泡向溶酶体和溶酶体相关细胞器(LROs)的运输以及这些细胞器的大小对于维持其功能至关重要。溶酶体运输调节因子(LYST)的破坏会导致切迪阿克-东综合征(CHS),这是一种罕见的常染色体隐性疾病,其特征为眼皮肤白化病、出血时间延长、严重免疫缺陷、反复细菌感染、神经功能障碍和噬血细胞性淋巴组织细胞增生症(HLH)。该综合征的典型诊断特征是所有细胞类型中的LROs增大,包括溶酶体、黑素小体、溶细胞颗粒和血小板致密体。观察到的最显著的CHS眼部病理变化是视网膜色素上皮(RPE)中黑素小体增大,这导致眼色素沉着分布异常,并导致畏光和视力下降。了解LYST的分子功能并鉴定其相互作用伙伴可能为CHS以及其他与LRO大小调节和/或囊泡运输相关的疾病(如哮喘、荨麻疹和亚马逊利什曼原虫感染)提供治疗靶点。