Mascotti F, Cáceres A, Pfenninger K H, Quiroga S
Instituto Investigación Médica Mercedes y Martín Ferreya, Córdoba, Argentina.
J Neurosci. 1997 Feb 15;17(4):1447-59. doi: 10.1523/JNEUROSCI.17-04-01447.1997.
Betagc is a beta-subunit variant of the insulin-like growth factor-1 (IGF-1) receptor highly enriched in growth cone membranes prepared by subcellular fractionation of fetal rat brain (). The present study is focused on the expression and on the cellular and subcellular distribution of betagc in developing neurons and differentiating PC12 cells. In the developing cerebral cortex and, at least at early stages, in cultured primary neurons, betagc expression was found to be correlated with neurite outgrowth. In PC12 cells betagc expression was nerve growth factor (NGF)-dependent and also paralleled neurite outgrowth. In contrast, beta-subunits of the insulin receptor and/or of other IGF-1 receptors ("betaP5"; detected with antibody AbP5) were downregulated as betagc expression increased. Immunofluorescence studies confirmed the enrichment of betagc at growth cones and demonstrated morphologically its spatial separation from betaP5, which is confined to the perikaryon. At the growth cone, betagc colocalizes and associates in a proximal region with microtubules, but it seems independent of the more peripheral microfilaments. Some betagc immunoreactivity is detected in the perinuclear region of PC12 cells, most likely the Golgi complex and its vicinity. betagc seems to emerge from the periphery of this structure in an apparently vesicular compartment distinct from that carrying synaptophysin to the growth cones. The facts that (1) betagc expression is correlated closely with neurite outgrowth, that (2) it is regulated in PC12 cells by a neurotrophin, NGF, and that (3) betagc is concentrated in the proximal growth cone region raise new questions regarding a possible role of IGF-1 receptors containing betagc in the regulation of neurite growth.
Betagc是胰岛素样生长因子-1（IGF-1）受体的β亚基变体，在通过胎鼠脑亚细胞分级分离制备的生长锥膜中高度富集。本研究聚焦于betagc在发育中的神经元和分化的PC12细胞中的表达以及细胞和亚细胞分布。在发育中的大脑皮层以及至少在早期阶段的培养原代神经元中，发现betagc表达与神经突生长相关。在PC12细胞中，betagc表达依赖于神经生长因子（NGF），并且也与神经突生长平行。相反，随着betagc表达增加，胰岛素受体和/或其他IGF-1受体的β亚基（“βP5”；用抗体AbP5检测）被下调。免疫荧光研究证实betagc在生长锥处富集，并在形态学上证明其与局限于核周体的βP5在空间上分离。在生长锥处，betagc在近端区域与微管共定位并结合，但它似乎独立于更外周的微丝。在PC12细胞的核周区域检测到一些betagc免疫反应性，最有可能是高尔基体及其附近区域。betagc似乎从这个结构的周边出现在一个明显的囊泡区室中，该囊泡区室与将突触素运送到生长锥的区室不同。以下事实：（1）betagc表达与神经突生长密切相关，（2）它在PC12细胞中受神经营养因子NGF调节，以及（3）betagc集中在近端生长锥区域，引发了关于含有betagc的IGF-1受体在神经突生长调节中可能作用的新问题。
