Zhong N A, Moroziewicz D N, Ju W, Wisniewski K E, Jurkiewicz A, Brown W T
Molecular Neurogenetic Diagnostic Laboratory, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, USA.
Neurogenetics. 2000 Sep;3(1):41-4. doi: 10.1007/pl00022978.
The lysosomal storage of lipofuscins is the common pathological feature that characterizes the infantile, late-infantile, juvenile (Batten's disease), and Finnish-variant neuronal ceroid lipofuscinosis (INCL, LINCL, JNCL and FNCL), which are due to mutations in the genes CLN1, CLN2, CLN3, and CLN5, respectively. The CLN1 and CLN2 genes encode lysosomal enzymes, but the CLN3 and CLN5 genes encode membrane-spanning proteins. Why deficiencies of lysosomal enzymes and membrane-spanning proteins produce similar clinical phenotypes and pathological changes is still unanswered. We hypothesize that CLN-encoded proteins may comprise a functional pathogenic pathway, in which protein associations may play important roles. To test this hypothesis, we studied protein-protein interactions among the CLN1-, CLN2-, and CLN3-encoded proteins using a yeast two-hybrid system. Our results provided no evidence that CLN-encoded proteins interact with each other. This suggests there may be unidentified components in NCL pathogenesis.
脂褐素的溶酶体储存是婴儿型、晚婴儿型、青少年型（巴滕病）和芬兰变异型神经元蜡样脂褐质沉积症（婴儿型神经元蜡样脂褐质沉积症、晚婴儿型神经元蜡样脂褐质沉积症、青少年型神经元蜡样脂褐质沉积症和芬兰型神经元蜡样脂褐质沉积症）的共同病理特征，这些病症分别是由CLN1、CLN2、CLN3和CLN5基因的突变引起的。CLN1和CLN2基因编码溶酶体酶，但CLN3和CLN5基因编码跨膜蛋白。溶酶体酶和跨膜蛋白的缺陷为何会产生相似的临床表型和病理变化仍未得到解答。我们推测，CLN编码的蛋白质可能构成一条功能性致病途径，其中蛋白质相互作用可能起重要作用。为了验证这一假设，我们使用酵母双杂交系统研究了CLN1、CLN2和CLN3编码的蛋白质之间的蛋白质-蛋白质相互作用。我们的结果没有提供CLN编码的蛋白质相互作用的证据。这表明神经元蜡样脂褐质沉积症发病机制中可能存在尚未确定的成分。
