Identification and characterization of splicing variants ofPLEKHA5 (Plekha5) during brain development.
Identification and characterization of splicing variants ofPLEKHA5 (Plekha5) during brain development.
复制标题
大脑发育过程中 PLEKHA5 (Plekha5) 剪接变体的鉴定和表征。
DOI：
10.1016/j.gene.2011.10.018
复制
发表时间：
2012
期刊：
影响因子：
3.5
通讯作者：
Wakamatsu N
中科院分区：
文献类型：
--
作者：
Yamada K;Nomura N;Yamano A;Yamada Y;Wakamatsu N
PLEKHA5(PLEKHA5)属于PLEKHA家族(PLEKHA1-6)，是Pleckstrin同源域蛋白家族中的第5个成员，但对该蛋白的性质研究还很少。我们已经鉴定并鉴定了两种形式的PLEKHA5mRNA。长型PLEKHA5(L-PLEKHA5)含32个外显子，编码1,282个氨基酸，在脑内特异表达；短型PLEKHA5(S-PLEKHA5)由L-PLEKHA5交替剪接产生，含26个外显子，编码1,116个氨基酸，广泛表达。这两种形式的蛋白质都含有可能的Trp-Trp(WW)和Pleckstrin Homology(PH)结构域，主要位于胞浆中。在小鼠脑中的发育和年龄依赖性表达研究表明，Plekha5是E13.5表达最丰富的蛋白，以S-Plekha5为主。随着总Plekha5水平的降低，L-Plekha5的水平逐渐升高，并且L-Plekha5在E17.5成为优势蛋白，并在整个成年期保持其优势。蛋白质-脂质重叠分析表明，PLEKHA5的PH结构域与PI3P、PI4P、PI5P和PI(3，5)P2特异地相互作用。这些结果提示，PLEKHA5(Plekha5)的S-L-转换可能通过与特定的磷脂酰肌醇结合而在脑发育中发挥重要作用。
PLEKHA5 (pleckstrin homology domain-containing protein family A, member 5) belongs to the PLEKHA family (PLEKHA1–6); however, the properties of this protein remain poorly characterized. We have identified and characterized two forms of PLEKHA5 mRNA. The long form of PLEKHA5 (L-PLEKHA5) contains 32 exons, encodes 1282 amino acids, and is specifically expressed in the brain; the short form of PLEKHA5 (S-PLEKHA5) is generated by alternative splicing of L-PLEKHA5, contains 26 exons, encodes 1116 amino acids, and is ubiquitously expressed. Both forms of the protein contain putative Trp–Trp (WW) and pleckstrin homology (PH) domains and are located mainly in the cytosol. Developmental and age-dependent expression studies in the mouse brain have shown that Plekha5 is the most abundantly expressed protein at E13.5 with S-Plekha5 dominancy. L-Plekha5 levels increased gradually with the decrease in total Plekha5 levels; moreover, L-Plekha5 became the dominant protein at E17.5, maintaining its dominance throughout adulthood. Protein-lipid overlay assays have indicated that the PH domain of PLEKHA5 specifically interacts with PI3P, PI4P, PI5P, and PI(3,5)P2. These results suggest that the S- to L-conversion of PLEKHA5 (Plekha5) may play an important role in brain development through association with specific phosphoinositides.