Identification of novel splicing variants of protein tyrosine phosphatase receptor type Z
Identification of novel splicing variants of protein tyrosine phosphatase receptor type Z
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DOI：
10.1093/jb/mvx042
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发表时间：
2017-11-01
影响因子：
2.7
通讯作者：
Noda, Masaharu
中科院分区：
文献类型：
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作者：
Fujikawa, Akihiro;Chow, Jeremy Pak Hong;Noda, Masaharu
蛋白酪氨酸磷酸酶受体Z型（PTPRZ，也称为PTP zeta或RPTP β）优先在中枢神经系统（CNS）中表达。PTPRZ在中枢神经系统发育和成人期的髓鞘形成、学习和记忆中起重要作用。迄今为止已经鉴定出PTPRZ的三种剪接异构体：两种受体型异构体PTPRZ- a和PTPRZ- b，以及一种分泌型异构体PTPRZ- s。我们在此鉴定了新的PTPRZ受体亚亚型，没有由外显子16编码的7个氨基酸序列。该序列形成了螺旋-螺旋-螺旋段的一部分，称为“楔形”结构，位于膜-近端蛋白酪氨酸磷酸酶结构域的n端区域。与均匀表达的传统受体异构体相比，缺失的异构体在大脑中表达，而在视网膜中不表达，这表明外显子16的组织特异性剪接。对PTPRZ细胞内区域的生化分析揭示了缺失形式的特征差异，即与突触后密度蛋白95 （PSD95）结合活性更强，突触后密度部分的富集程度高于全长形式。此外，外显子16缺失形式在体外表现出更高的催化效率。这些结果表明，PTPRZ的亚同工型由于楔状结构的变化而具有不同的功能。
Protein tyrosine phosphatase receptor type Z (PTPRZ, also known as PTP zeta or RPTP beta) is preferentially expressed in the central nervous system (CNS). PTPRZ plays important roles during development and adulthood in CNS myelination, learning and memory. Three splicing isoforms for PTPRZ have been identified to date: two receptor type isoforms, PTPRZ-A and PTPRZ-B, and one secretory isoform, PTPRZ-S. We herein identified novel PTPRZ receptor sub-isoforms without a seven-amino acid sequence encoded by exon 16. This sequence forms a part of the helix-turn-helix segment called the 'wedge' structure, which is located at the N-terminal region in the membrane-proximal protein tyrosine phosphatase domain. In contrast to conventional receptor isoforms with uniform expression, the deleted isoforms were expressed in the brain, but not in the retina, indicating the tissue-specific splicing of exon 16. Biochemical analyses of PTPRZ intracellular regions revealed differences in the characteristics of the deleted form, namely, stronger binding activity to postsynaptic density protein 95 (PSD95) and greater enrichment in the postsynaptic density fraction than the full-length form. Furthermore, the exon 16-deleted form exhibited higher catalytic efficiency in vitro. These results suggest that sub-isoforms of PTPRZ have different functions because of variations in the wedge structure.