Portales-Casamar Elodie, Briançon-Marjollet Anne, Fromont Sylvie, Triboulet Robinson, Debant Anne
CRBM-CNRS, FRE 2593, 1919 Route de Mende, 34293 Montpellier, France.
Biol Cell. 2006 Mar;98(3):183-93. doi: 10.1042/BC20050009.
The large family of GEFs (guanine nucleotide-exchange factors) for Rho GTPases activate the GTPases by accelerating their GDP/GTP exchange. The multidomain protein Trio is the founding member of an intriguing subfamily of Rho-GEFs exhibiting two Rho-GEF and numerous additional domains. The members of the Trio family play an important role in neuronal physiology, and their structural organization is very well conserved through evolution. It has previously been shown that all the members, except mammalian Trio, display several isoforms, the functions of which have been well established.
In this study, we have identified, by a combination of different approaches, novel Trio isoforms that have been generated by alternative splicing, giving rise to proteins that exhibit one or two Rho-GEF domains (GEFDs). These isoforms are specifically expressed in the nervous system, at a higher level than the full-length Trio, which is ubiquitously expressed. In addition, we show that all the GEFD1-containing isoforms induce neurite outgrowth in neuroblastoma cells.
We have identified neuronal specific isoforms of Trio which could be essential for Trio function in neuronal morphology.
Rho GTP酶的鸟嘌呤核苷酸交换因子（GEF）大家族通过加速GDP/GTP交换来激活GTP酶。多结构域蛋白Trio是Rho-GEFs一个有趣亚家族的创始成员，具有两个Rho-GEF结构域和许多其他结构域。Trio家族成员在神经元生理学中发挥重要作用，其结构组织在进化过程中高度保守。此前研究表明，除哺乳动物Trio外，所有成员都有几种亚型，其功能已得到充分证实。
在本研究中，我们通过多种方法相结合，鉴定出了由可变剪接产生的新型Trio亚型，这些亚型产生的蛋白质具有一个或两个Rho-GEF结构域（GEFD）。这些亚型在神经系统中特异性表达，表达水平高于广泛表达的全长Trio。此外，我们还表明，所有含GEFD1的亚型都能诱导神经母细胞瘤细胞的神经突生长。
我们鉴定出了Trio的神经元特异性亚型，它们可能对Trio在神经元形态中的功能至关重要。
