Department of Cell Biology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, 6525 GA Nijmegen, The Netherlands.
Int J Biol Sci. 2011;7(7):978-91. doi: 10.7150/ijbs.7.978. Epub 2011 Aug 9.
Mouse protein tyrosine phosphatase PTPBR7 is a receptor-like, transmembrane protein that is localized on the surface of neuronal cells. Its protein phosphatase activity is reduced upon multimerization, and PTPBR7-deficient mice display motor coordination defects. Extracellular molecules that may influence PTPBR7 activity, however, remain to be determined. We here show that the PTPBR7 extracellular domain binds to highly myelinated regions in mouse brain, in particular the white matter tracks in cerebellum. PTPBR7 deficiency does not alter this binding pattern, as witnessed by RAP in situ staining of Ptprr⁻/⁻ mouse brain sections. Additional in situ and in vitro experiments also suggest that sugar moieties of heparan sulphate and chondroitin sulphate glycosaminoglycans are not critical for PTPBR7 binding. Candidate binding proteins were affinity-purified exploiting the PTPBR7 extracellular domain and identified by mass spectrometric means. Results support the suggested link between PTPRR isoforms and cerebellar calcium ion homeostasis, and suggest an additional role in the process of cell-cell adhesion.
鼠蛋白酪氨酸磷酸酶 PTPBR7 是一种受体样跨膜蛋白，位于神经元细胞表面。其蛋白磷酸酶活性在多聚化后降低，PTPBR7 缺陷小鼠表现出运动协调缺陷。然而，仍有待确定可能影响 PTPBR7 活性的细胞外分子。我们在这里表明，PTPBR7 的细胞外结构域与小鼠大脑中高度髓鞘化的区域结合，特别是小脑的白质轨迹。PTPBR7 缺乏不会改变这种结合模式，如 Ptprr⁻/⁻ 小鼠脑切片的 RAP 原位染色所证明的那样。额外的原位和体外实验也表明，硫酸乙酰肝素和软骨素硫酸糖胺聚糖的糖基部分对于 PTPBR7 的结合不是关键的。利用 PTPBR7 的细胞外结构域，通过亲和纯化来分离候选结合蛋白，并通过质谱手段进行鉴定。结果支持 PTPRR 同工型与小脑钙离子动态平衡之间的关联，并提示其在细胞-细胞黏附过程中具有额外的作用。
