Rat wild-type parathyroid hormone receptor (PTH-R) and mutant PTH-R(P132L) show the different intracellular localization in vitro.
Rat wild-type parathyroid hormone receptor (PTH-R) and mutant PTH-R(P132L) show the different intracellular localization in vitro.
复制标题
大鼠野生型甲状旁腺激素受体（PTH-R）和突变型PTH-R（P132L）在体外表现出不同的细胞内定位。
DOI：
10.2220/biomedres.29.61
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发表时间：
2008
期刊：
影响因子：
--
通讯作者：
N. Amizuka
中科院分区：
文献类型：
--
作者：
J. Shimomura;Sobhan Ubaidus;Paulo Hl Freitas;Minqi Li;Y. Ishida;N. Saito;Kimimitsu Oda;S. Shimooka;N. Amizuka
甲状旁腺激素（PTH）/甲状旁腺激素相关肽（PTHrP）受体132位的脯氨酸被亮氨酸取代，即，PTH-R在人类Blomstrand致死性软骨发育不良中被发现。由于这种类型的软骨发育不良的骨骼畸形似乎损害了受体与其配体的结合，我们研究了大鼠PTH-R携带P132 L突变（PTH-R（P132 L））将导致异常细胞内定位的可能性。用含有编码野生型PTH-R或突变型PTH-R（P132 L）的cDNA的表达载体转染成骨细胞MC 3 T3-E1细胞。表达野生型PTH-R的细胞产生一种分子量为66.3 kDa的受体蛋白，其免疫反应性主要位于细胞表面。而PTH-R（P132 L）在细胞表面几乎检测不到，但在粗面内质网中积累。与这种定位一致，表达突变受体的细胞未能产生环AMP响应PTH。此外，与野生型对应物相比，66.3 kDa条带的强度明显较弱，表明PTH-R（P132 L）在转染细胞中易于降解。总之，这些发现表明PTH-R（P132 L）向细胞表面的缺陷转运可能是Blomstrand软骨发育不良的分子基础。
A replacement of proline with leucine at position 132 of the receptor for parathyroid hormone (PTH)/parathyroid hormone-related peptide (PTHrP), i.e., PTH-R, has been discovered in human Blomstrand's lethal chondrodysplasia. As skeletal deformities in this type of chondrodysplasia appear to compromise the receptor binding to its ligands, we examined the possibility that rat PTH-R carrying P132L mutation (PTH-R(P132L)) would result in abnormal intracellular localization. Osteoblastic MC3T3-E1 cells were transfected with expression vectors containing cDNAs encoding either wild-type PTH-R or mutant PTH-R(P132L). The cells expressing the wild-type PTH-R produced a receptor protein with a molecular mass of 66.3 kDa, which localized its immunoreactivity mainly on the cell surfaces. In contrast, the PTH-R(P132L) was hardly detected on the cell surfaces, but accumulated within the rough-surfaced endoplasmic reticulum. Consistent with this localization, the cells expressing the mutant receptor failed to generate cyclic AMP in response to PTH. Furthermore, a remarkably weaker intensity of the 66.3 kDa band compared with the wild-type counterpart suggests that PTH-R(P132L) is prone to degradation in the transfected cells. In summary, these findings indicate that defective transport of PTH-R(P132L) to the cell surface would be a molecular basis for Blomstrand's chondrodysplasia.
影响因子：
10.5
作者：
KARAPLIS, AC;LUZ, A;MULLIGAN, RC
通讯作者：
MULLIGAN, RC
影响因子：
56.9
作者：
JUPPNER, H;ABOUSAMRA, AB;SEGRE, GV
通讯作者：
SEGRE, GV