Temporal expression and mitochondrial localization of a Foxp2 isoform lacking the forkhead domain in developing Purkinje cells.
Temporal expression and mitochondrial localization of a Foxp2 isoform lacking the forkhead domain in developing Purkinje cells.
复制标题
发育中的浦肯野细胞中缺少叉头结构域的 Foxp2 亚型的时间表达和线粒体定位。
DOI：
10.1111/j.1471-4159.2011.07524.x
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发表时间：
2012
期刊：
影响因子：
4.7
通讯作者：
et al.
中科院分区：
文献类型：
--
作者：
Tanabe Y;et al.
J. Neurochem.(2012)122, 72–80.AbstractFOXP2 是一种含有叉头盒的转录因子，与 FOXP 家族成员形成同源或异源二聚体并定位于细胞核，而 FOXP2(R553H) 包含与言语/语言障碍相关的突变，其特点是 DNA 结合活性降低以及细胞质和细胞核定位。除了功能丧失突变之外，FOXP2(R553H) 还可能作为功能获得突变来抑制 FOXP2 亚型的功能，包括缺乏叉头结构域的 FOXP2Ex10+。 Foxp2(R552H) 敲入的小鼠幼仔表现出超声发声受损和浦肯野细胞树突发育不良。然而，Foxp2 同种型在发育中浦肯野病中的表达尚不清楚。 “顶端细胞质肿胀”（线粒体丰富的区域是出芽过程的来源）的出现与浦肯野细胞的树突发育相关。在本研究中，我们重点关注位于顶端细胞质肿胀的 Foxp2 同工型，并鉴定了两种缺乏叉头结构域的同工型：Foxp2Ex12+ 和 Foxp2Ex15。它们部分定位于包括线粒体的膜部分。 Foxp2Ex12+ 主要定位于星状阶段 (P2-P4) 早期发育的浦肯野细胞的顶端细胞质肿胀。通过免疫电子显微镜分析证实了浦肯野细胞中 Foxp2Ex12+ 的线粒体定位。 Foxp2Ex12+ 可能在浦肯野细胞的树突发育中发挥作用。
J. Neurochem.(2012)122, 72–80.AbstractFOXP2, a forkhead box‐containing transcription factor, forms homo‐ or hetero‐dimers with FOXP family members and localizes to the nucleus, while FOXP2(R553H), which contains a mutation related to speech/language disorders, features reduced DNA binding activity and both cytoplasmic and nuclear localization. In addition to being a loss‐of‐function mutation, it is possible that FOXP2(R553H) also may act as a gain‐of‐function mutation to inhibit the functions of FOXP2 isoforms including FOXP2Ex10+ lacking forkhead domain.Foxp2(R552H)knock‐in mouse pups exhibit impaired ultrasonic vocalization and poor dendritic development in Purkinje cells. However, expressions of Foxp2 isoforms in the developing Purkinje are unclear. The appearance of ‘apical cytoplasmic swelling’ (mitochondria‐rich regions that are the source of budding processes) correlates with dendritic development of Purkinje cells. In the present study, we focused on Foxp2 isoforms localizing to the apical cytoplasmic swelling and identified two isoforms lacking forkhead domain: Foxp2Ex12+ and Foxp2Ex15. They partly localized to the membrane fraction that includes mitochondria. Foxp2Ex12+ mainly localized to the apical cytoplasmic swelling in early developing Purkinje cells at the stellate stage (P2–P4). Mitochondrial localization of Foxp2Ex12+ in Purkinje cells was confirmed by immune‐electron microscopic analysis. Foxp2Ex12+ may play a role in dendritic development in Purkinje cells.