Institute for Research in Biomedicine, Parc Cientific de Barcelona, Barcelona, Spain.
PLoS One. 2010 Aug 10;5(8):e12003. doi: 10.1371/journal.pone.0012003.
Neural development and plasticity are regulated by neural adhesion proteins, including the polysialylated form of NCAM (PSA-NCAM). Podocalyxin (PC) is a renal PSA-containing protein that has been reported to function as an anti-adhesin in kidney podocytes. Here we show that PC is widely expressed in neurons during neural development. Neural PC interacts with the ERM protein family, and with NHERF1/2 and RhoA/G. Experiments in vitro and phenotypic analyses of podxl-deficient mice indicate that PC is involved in neurite growth, branching and axonal fasciculation, and that PC loss-of-function reduces the number of synapses in the CNS and in the neuromuscular system. We also show that whereas some of the brain PC functions require PSA, others depend on PC per se. Our results show that PC, the second highly sialylated neural adhesion protein, plays multiple roles in neural development.
神经发育和可塑性受神经黏附蛋白调节，包括 NCAM 的多涎酸化形式（PSA-NCAM）。足细胞蛋白聚糖（PC）是一种含有 PSA 的肾脏蛋白聚糖，已有研究表明其在肾脏足细胞中作为一种抗黏附分子发挥作用。本研究表明，PC 在神经发育过程中广泛表达于神经元。神经 PC 与 ERM 蛋白家族相互作用，并与 NHERF1/2 和 RhoA/G 相互作用。体外实验和 podxl 缺陷小鼠的表型分析表明，PC 参与轴突生长、分支和轴突聚集，PC 功能丧失会减少中枢神经系统和神经肌肉系统中的突触数量。我们还发现，虽然大脑 PC 的某些功能需要 PSA，但其他功能则依赖于 PC 本身。我们的结果表明，作为第二个高度涎酸化的神经黏附蛋白，PC 在神经发育中发挥多种作用。
