Pearce D A
Center for Aging and Developmental Biology, Department of Biochemistry and Biophysics, University of Rochester School of Medicine and Dentistry, New York 14642, USA.
J Neurosci Res. 2000 Jan 1;59(1):19-23.
Although the CLN3 gene for Batten disease, the most common inherited neurovisceral storage disease of childhood, was identified in 1995, the function of the corresponding protein still remains elusive. A key to understanding the pathology of this devastating disease will be to elucidate the function of CLN3 at the molecular level. CLN3 has proven difficult to study, as it is predicted to be a membrane protein, and is of apparently low abundance in cells. Different groups have reported differing subcellular localization of CLN3. The purpose of this review is to critically examine the various cell biological approaches undertaken to localize CLN3 and to piece together a potential function for CLN3 in neuronal cells. The most likely conclusion of this is that CLN3 is a lysosomal/endosomal protein that is trafficked through the endoplasmic reticulum (ER) and Golgi. Furthermore, studies are required to confirm whether CLN3 has a potential role in the recycling of synaptic vesicles through the endosome/lysosome.
尽管1995年就已确定导致儿童期最常见的遗传性神经内脏贮积病——贝敦氏病的CLN3基因，但相应蛋白质的功能仍然难以捉摸。理解这种毁灭性疾病病理的关键在于在分子水平上阐明CLN3的功能。事实证明，CLN3很难研究，因为据预测它是一种膜蛋白，且在细胞中的丰度明显较低。不同的研究小组报告了CLN3在亚细胞定位上的差异。这篇综述的目的是批判性地审视为确定CLN3定位所采用的各种细胞生物学方法，并拼凑出CLN3在神经元细胞中的潜在功能。最有可能的结论是，CLN3是一种通过内质网（ER）和高尔基体运输的溶酶体/内体蛋白。此外，还需要进行研究以确认CLN3是否在通过内体/溶酶体回收突触小泡方面具有潜在作用。
