6月22日,，Cell雜志報道：上海神經(jīng)科學(xué)研究所張旭研究組發(fā)現(xiàn)成纖維細(xì)胞生長因子13在神經(jīng)細(xì)胞中作為微管穩(wěn)定蛋白發(fā)揮重要調(diào)節(jié)功能,。
分泌性成纖維細(xì)胞生長因子（FGFs）和其受體在神經(jīng)系統(tǒng)發(fā)育的早期階段發(fā)揮調(diào)節(jié)功能,。 FGF13,，是FGF家族的非分泌性蛋白質(zhì),。它在神經(jīng)發(fā)展過程中表達(dá)于大腦皮質(zhì)神經(jīng)元,，是綜合征性及非特異性X染色體連鎖性智障（XLMR）的候選基因,。然而,，其在神經(jīng)發(fā)育過程中的功能尚不清楚,。
本研究表明，F(xiàn)GF13在細(xì)胞內(nèi)作為軸突必須的微管穩(wěn)定蛋白并在大腦皮層神經(jīng)細(xì)胞遷移中起著引導(dǎo)的重要作用,。 FGF13富集于軸突生長錐,，并直接與微管相互作用。此外,，F(xiàn)GF13聚合微管蛋白并穩(wěn)定微管,。 敲除FGF13基因可損害神經(jīng)元極化并增加軸突的分支化和引導(dǎo)生長作用。 FGF13的基因缺失可導(dǎo)致小鼠大腦皮層和海馬的神經(jīng)細(xì)胞遷移缺陷,。 FGF13缺陷小鼠也表現(xiàn)出學(xué)習(xí)和記憶能力的減退,。這與XLMR患者的智力殘疾是想對應(yīng)的。
總之,，本研究揭示了FGF13在神經(jīng)細(xì)胞極化和遷移中的重要作用,，為XLMR等相關(guān)疾病的進(jìn)一步研究帶來新的重要啟示。（生物谷bioon.com）
doi:10.1016/j.cell.2011.10.017
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Fibroblast Growth Factor 13 Is a Microtubule-Stabilizing Protein Regulating Neuronal Polarization and Migration
Qing-Feng Wu, Liu Yang, Shuai Li, Qiong Wang, Xiao-Bin Yuan, Xiang Gao,Xu Zhang
Secretory fibroblast growth factors (FGFs) and their receptors are known for their regulatory function in the early stages of neural development. FGF13, a nonsecretory protein of the FGF family, is expressed in cerebral cortical neurons during development and is a candidate gene for syndromal and nonspecific forms of X-chromosome-linked mental retardation (XLMR). However, its function during development remains unclear. We show that FGF13 acts intracellularly as a microtubule-stabilizing protein required for axon and leading process development and neuronal migration in the cerebral cortex. FGF13 is enriched in axonal growth cones and interacts directly with microtubules. Furthermore, FGF13 polymerizes tubulins and stabilizes microtubules. The loss of FGF13 impairs neuronal polarization and increases the branching of axons and leading processes. Genetic deletion of FGF13 in mice results in neuronal migration defects in both the neocortex and the hippocampus. FGF13-deficient mice also exhibit weakened learning and memory, which is correlated to XLMR patients' intellectual disability.
