根據(jù)一篇發(fā)布在Genetics上的文章,，亞拉巴馬大學(xué)的科學(xué)家在線蟲C. elegans中識別一種關(guān)鍵的分子開關(guān)，其能控制γ氨基丁酸（GABA）的運輸,。
研究人員表示,，他們希望這項研究能夠加速癲癇遺傳因子的識別。同時,，這項研究結(jié)果或有助于在未來開發(fā)出控制或預(yù)防癲癇的新方法,。
研究人員使用能影響神經(jīng)元活性的藥物對線蟲進(jìn)行試驗，并結(jié)合在人類和線蟲中共有的遺傳因子的DNA變異,。結(jié)果表明,，線蟲神經(jīng)元活性的改變導(dǎo)致了反復(fù)的抽搐，這種現(xiàn)象和癲癇表現(xiàn)出的癥狀是相似的,。研究人員在顯微鏡下觀察這些抽搐,，并根據(jù)試驗視頻估計神經(jīng)元改變的嚴(yán)重程度。
然后,，研究人員使用綠色熒光蛋白來標(biāo)記細(xì)胞位點,，跟蹤GABA在神經(jīng)元中的傳遞,。標(biāo)記物使得研究人員觀察到了一種特殊的遺傳因子，其能夠?qū)е律窠?jīng)元出現(xiàn)異常的GABA移動,，當(dāng)線蟲表現(xiàn)出癲癇癥狀時,。
盡管在新藥開發(fā)之前還有大量的工作要進(jìn)行，但這項發(fā)現(xiàn)為患有該類疾病的患者帶來了新的希望,。（生物谷Bioon.com）
生物谷推薦原始出處：
Genetics, Vol. 183, 1357-1372, December 2009 doi:10.1534/genetics.109.106880
Pharmacogenetic Analysis Reveals a Post-Developmental Role for Rac GTPases in Caenorhabditis elegans GABAergic Neurotransmission
Cody J. Locke*,1,2, Bwarenaba B. Kautu*,1, Kalen P. Berry*, S. Kyle Lee*, Kim A. Caldwell*,,3 and Guy A. Caldwell*,,3
* Department of Biological Sciences, The University of Alabama, Tuscaloosa, Alabama 35487 and Departments of Neurobiology and Neurology and Center for Neurodegeneration and Experimental Therapeutics, University of Alabama, Birmingham, Alabama 35294
3 Corresponding authors: Department of Biological Sciences, The University of Alabama, Box
The nerve-cell cytoskeleton is essential for the regulation of intrinsic neuronal activity. For example, neuronal migration defects are associated with microtubule regulators, such as LIS1 and dynein, as well as with actin regulators, including Rac GTPases and integrins, and have been thought to underlie epileptic seizures in patients with cortical malformations. However, it is plausible that post-developmental functions of specific cytoskeletal regulators contribute to the more transient nature of aberrant neuronal activity and could be masked by developmental anomalies. Accordingly, our previous results have illuminated functional roles, distinct from developmental contributions, for Caenorhabditis elegans orthologs of LIS1 and dynein in GABAergic synaptic vesicle transport. Here, we report that C. elegans with function-altering mutations in canonical Rac GTPase-signaling-pathway members demonstrated a robust behavioral response to a GABAA receptor antagonist, pentylenetetrazole. Rac mutants also exhibited hypersensitivity to an acetylcholinesterase inhibitor, aldicarb, uncovering deficiencies in inhibitory neurotransmission. RNA interference targeting Rac hypomorphs revealed synergistic interactions between the dynein motor complex and some, but not all, members of Rac-signaling pathways. These genetic interactions are consistent with putative Rac-dependent regulation of actin and microtubule networks and suggest that some cytoskeletal regulators cooperate to uniquely govern neuronal synchrony through dynein-mediated GABAergic vesicle transport in C. elegans.
