Overexpression of GAP-43 reveals unexpected properties of hippocampal mossy fibers.
Overexpression of GAP-43 reveals unexpected properties of hippocampal mossy fibers.
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GAP-43 的过度表达揭示了海马苔藓纤维的意外特性。
DOI：
10.1002/hipo.20668
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发表时间：
2010
期刊：
影响因子：
3.5
通讯作者：
Routtenberg,Aryeh
中科院分区：
文献类型：
--
作者：
Rekart,JeromeL;Routtenberg,Aryeh
苔藓纤维（MF）系统靶向透明层（SL）中的CA 3锥体细胞的顶树突。在过表达生长相关蛋白GAP-43的小鼠中，这些MF明显异位生长到定向层（SO）中，靶向这些相同锥体细胞的基底树突（艾格纳（Aigner）et al.（1995）Cell 83：269-278）。这是我们所知的将GAP-43表达增加与中央轴突生长联系起来的第一个证据。在此，我们研究了艾格纳等人的转基因小鼠，但不能证实这种生长为SO。然而，使用定量方法，我们确实观察到MF通常靶向的区域内的生长增强，例如CA 3a区域中的SL。这些对比的结果使我们研究MF与双免疫染色使用免疫组化标记MF，锌转运蛋白，ZnT 3，可视化转基因GAP-43的共定位内MF。出乎意料的是，使用荧光和共聚焦显微镜，我们无法检测到共定位的GAP-43阳性轴突与ZnT 3阳性MF轴突内的MF途径，无论是在该地区的MF轴突或在SL，其中MF终端是丰富的。与此相反，质膜相关的突触前标记SNAP-25没有共定位与转基因GAP-43阳性终端的SL。突触素（囊泡相关的突触前末端标记物）与ZnT 3共定位，但似乎没有与GAP-43共定位。本研究结果提出了关于颗粒细胞特性和MF机制的重要问题，这些机制差异调节成年海马轴突重塑：（1）由于颗粒细胞的蛋白质表达至少有两个群体，这表明存在着一种内在的颗粒细胞表达的异质性，超出了成年神经发生的贡献;（2）给出了在相邻的不含GAP-43的MF中过表达GAP-43的小鼠中诱导生长的现有证据，可能存在一种迄今为止尚未探索的轴突间通讯机制。
The mossy fiber (MF) system targets the apical dendrites of CA3 pyramidal cells in the stratum lucidum (SL). In mice overexpressing the growth-associated protein GAP-43 there is an apparent ectopic growth of these MFs into the stratum oriens (SO) targeting the basal dendrites of these same pyramidal cells (Aigner et al.(1995) Cell 83: 269–278). This is the first evidence to our knowledge that links increased GAP-43 expression with growth of central axons. Here we studied the Aigner et al. transgenic mice but were unable to confirm such growth into SO. However, using quantitative methods we did observe enhanced growth within the regions normally targeted by MFs, for example, the SL in the CA3a region. These contrasting results led us to study MFs with double-immunostaining using an immunohistochemical marker for MFs, the zinc transporter, ZnT3, to visualize the colocalization of transgenic GAP-43 within MFs. Unexpectedly, using both fluorescence and confocal microscopy, we were unable to detect colocalization of GAP-43-positive axons with ZnT3-positive MF axons within the MF pathways, either in the region of the MF axons or in the SL, where MF terminals are abundant. In contrast, the plasma membrane-associated presynaptic marker SNAP-25 did colocalize with transgenic GAP-43-positive terminals in the SL. Synaptophysin, the vesicle-associated presynaptic terminal marker, colocalized with ZnT3 but did not appear to colocalize with GAP-43. The present findings raise important questions about the properties of granule cells and the MF mechanisms that differentially regulate axonal remodeling in the adult hippocampus:(1) Because there appears to be at least two populations of granule cells defined by their differential protein expression, this points to the existence of an intrinsic heterogeneity of granule cell expression beyond that contributed by adult neurogenesis;(2) Giventhe present evidence that growth is induced in mice overexpressing GAP-43 in adjacent non-GAP-43 containing MFs, the potential exists for a heretofore unexplored interaxonal communication mechanism.© 2009 Wiley-Liss, Inc.