PRECEREBELLIN IS A CEREBELLUM-SPECIFIC PROTEIN WITH SIMILARITY TO THE GLOBULAR DOMAIN OF COMPLEMENT CLQ B-CHAIN
PRECEREBELLIN IS A CEREBELLUM-SPECIFIC PROTEIN WITH SIMILARITY TO THE GLOBULAR DOMAIN OF COMPLEMENT CLQ B-CHAIN
复制标题
DOI：
10.1073/pnas.88.3.1069
复制
发表时间：
1991-02-01
影响因子：
11.1
通讯作者：
MORGAN, JI
中科院分区：
文献类型：
--
作者：
URADE, Y;OBERDICK, J;MORGAN, JI
小脑含有一个十六肽，称为小脑蛋白，其在人类和鸡的序列中是保守的。 三个独立的，重叠的cDNA克隆已被分离出的人小脑的cDNA文库编码的cerebellin序列。 最长的克隆编码一种193个氨基酸的蛋白质，我们称之为前小脑素。 该蛋白质与人补体成分C1 q的B链的球状（非胶原样）区域具有显著的相似性（31.3%同一性，52.2%相似性）。 相关性区域延伸超过位于两种蛋白质的羧基末端的几乎等于145个氨基酸。 与Clq B链不同，在前小脑肽的氨基末端区域不存在胶原样基序。 前小脑肽的氨基末端含有三个可能的N-连接糖基化位点。虽然疏水氨基酸在氨基末端聚集，但它们不符合经典的信号肽基序，并且从cDNA序列中预测没有其他明显的跨膜结构域。cDNA预测小脑肽两侧是Val-Arg和Glu-Pro残基。 因此，cerebellin不是通过在许多神经肽前体中看到的经典的二元氨基酸蛋白水解切割机制从precerebellin中释放出来的。 在北方（RNA）印迹中，小脑中有四种不同大小（1.8、2.3、2.7和3.0倍）的前小脑素转录本。 这些转录本在其他大脑区域和神经结构中以非常低或不可检测的水平存在。 在大鼠、小鼠和人类小脑中也发现了类似的小脑蛋白前体转录物模式。此外，小鼠的部分基因组片段在北方印迹中显示与人cDNA克隆相同的条带。 在大鼠发育过程中，小脑肽前体的转录水平反映小脑肽。 出生时观察到低水平的前小脑素mRNA。 从产后第1天到第8天，水平适度增加，然后在第5天到第15天之间急剧增加，并最终在第21天到第56天之间达到峰值。 由于小脑样免疫反应性与浦肯野细胞突触后结构，这些数据提出了有趣的可能性有关的功能小脑前体突触生理学。
The cerebellum contains a hexadecapeptide, termed cerebellin, that is conserved in sequence from human to chicken. Three independent, overlapping cDNA clones have been isolated from a human cerebellum cDNA library that encode the cerebellin sequence. The longest clone codes for a protein of 193 amino acids that we term precerebellin. This protein has a significant similarity (31.3% identity, 52.2% similarity) to the globular (non-collagen-like) region of the B chain of human complement component C1q. The region of relatedness extends over almost-equal-to 145 amino acids located in the carboxyl terminus of both proteins. Unlike Clq B chain, no collagen-like motifs are present in the amino-terminal regions of precerebellin. The amino terminus of precerebellin contains three possible N-linked glycosylation sites. Although hydrophobic amino acids are clustered at the amino terminus, they do not conform to the classical signal-peptide motif, and no other obvious membrane-spanning domains are predicted from the cDNA sequence. The cDNA predicts that the cerebellin peptide is flanked by Val-Arg and Glu-Pro residues. Therefore, cerebellin is not liberated from precerebellin by the classical dibasic amino acid proteolytic-cleavage mechanism seen in many neuropeptide precursors. In Northern (RNA) blots, precerebellin transcripts, with four distinct sizes (1.8, 2.3, 2.7, and 3.0 kilobases), are abundant in cerebellum. These transcripts are present at either very low or undetectable levels in other brain areas and extraneural structures. A similar pattern of cerebellin precursor transcripts are seen in rat, mouse, and human cerebellum. Furthermore, a partial genomic fragment from mouse shows the same bands in Northern blots as the human cDNA clone. During rat development, precerebellin transcripts mirror the level of cerebellin peptide. Low levels of precerebellin mRNA are seen at birth. Levels increase modestly from postpartum day 1 to 8, then increase more dramatically between day 5 and 15, and eventually reach peak values between day 21 and 56. Because cerebellin-like immunoreactivity is associated with Purkinje cell postsynaptic structures, these data raise interesting possibilities concerning the function of the cerebellin precursor in synaptic physiology.