Zahn T R, Macmorris M A, Dong W, Day R, Hutton J C
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA.
J Comp Neurol. 2001 Jan 1;429(1):127-43. doi: 10.1002/1096-9861(20000101)429:1<127::aid-cne10>3.0.co;2-h.
The closely related mammalian proteins IA-2 and phogrin are protein tyrosine phosphatase-like receptor proteins spanning the membrane of dense core vesicles of neuroendocrine tissues. They are of interest as molecular components of the secretory machinery and as major targets of autoimmunity in type I diabetes mellitus. The Caenorhabditis elegans genome has a single copy of an IA-2/phogrin homolog ida-1 III (islet cell diabetic autoantigen), which encodes the ida-1 (B0244.2) gene product as a series of 12 exons over a 10-kb region of chromosome III. The full-length sequence of the ida-1 cDNA encoded a 767-amino acid type 1 transmembrane protein of 87 kDa. The PTP catalytic site consensus sequence of IDA-1, like IA-2 and phogrin, diverged and would not be active. Expression of green fluorescent protein (GFP) under the ida-1 gene promoter showed activity in a subset of around 30 neurons with sensory functions and the uv1 cells of the vulva in hermaphrodites. Males showed additional expression in male-specific neurons. In situ experiments in rat brain showing the distribution of IA-2 and phogrin suggested a complimentary and overlapping pattern compared with the proprotein convertases PC1 and PC2. In C. elegans, IDA-1-expressing cells comprised a subset of those expressing the PC2 homolog KPC-2 (C51E3. 7), consistent with IDA-1 being a component of neuropeptide-containing dense core vesicles. The results support the hypothesis that C. elegans IDA-1 is the functional homolog of IA-2 and phogrin in mammals. Analysis of the function of IDA-1 should contribute to our understanding of the function of these proteins in signal transduction, vesicle locomotion, and exocytosis.
密切相关的哺乳动物蛋白IA-2和phogrin是蛋白酪氨酸磷酸酶样受体蛋白，跨越神经内分泌组织致密核心囊泡的膜。它们作为分泌机制的分子成分以及1型糖尿病自身免疫的主要靶点而备受关注。秀丽隐杆线虫基因组有一个IA-2/phogrin同源物ida-1 III（胰岛细胞糖尿病自身抗原）的单拷贝，其在III号染色体10 kb区域内将ida-1（B0244.2）基因产物编码为一系列12个外显子。ida-1 cDNA的全长序列编码了一个87 kDa的767个氨基酸的1型跨膜蛋白。与IA-2和phogrin一样，IDA-1的PTP催化位点共有序列发生了分歧，没有活性。在ida-1基因启动子下绿色荧光蛋白（GFP）的表达在约30个具有感觉功能的神经元亚群以及雌雄同体动物外阴的uv1细胞中显示出活性。雄性在雄性特异性神经元中表现出额外的表达。大鼠脑中显示IA-2和phogrin分布的原位实验表明，与前体蛋白转化酶PC1和PC2相比，存在互补和重叠模式。在秀丽隐杆线虫中，表达IDA-1的细胞包含那些表达PC2同源物KPC-2（C51E3.7）的细胞亚群，这与IDA-1作为含神经肽致密核心囊泡的成分一致。这些结果支持了秀丽隐杆线虫IDA-1是哺乳动物中IA-2和phogrin功能同源物的假设。对IDA-1功能的分析应有助于我们理解这些蛋白在信号转导、囊泡运动和胞吐作用中的功能。
