中国神经再生研究(英文版) ›› 2021, Vol. 16 ›› Issue (10): 1994-1995.doi: 10.4103/1673-5374.308086

• 观点:神经损伤修复保护与再生 • 上一篇    下一篇

Slc7a5神经发育调控

  

  • 出版日期:2021-10-15 发布日期:2021-03-19

Slc7a5 regulation of neural development

Aidan M. Sokolov, David M. Feliciano*   

  1. Department of Biological Sciences, Clemson University, Clemson, SC, USA
  • Online:2021-10-15 Published:2021-03-19
  • Contact: David M. Feliciano, PhD,dfelici@clemson.edu.
  • Supported by:
    This work was supported by a grant from 
    the National Institutes of Health, 
    No. R15 NS096562/NS/NINDS NIH HHS/United States (to DMF).

摘要:

Neural Regen ResSlc7a5在调节mTORC1活性和神经元发育中的关键作用

膜转运蛋白因其跨生物膜转运分子的能力及其在神经系统疾病中的作用而备受关注。这类转运蛋白之一就是溶质载体(SLC)家族成员。SLC转运蛋白可转运包括神经递质、脂肪酸、氨基酸和无机离子在内的所有分子,在为细胞提供必需资源方面承担着不可或缺的作用。举例来说,氨基酸由SLC家族成员转运。Slc7a5SLC家族成员之一,可以转运包括亮氨酸在内的大中性和支链氨基酸。Slc7a5Slc3a2形成异源二聚体,逆向转运氨基酸,从而共同承担氨基酸反转运蛋白的作用。包括亮氨酸、谷氨酰胺以及精氨酸在内的氨基酸通过激活蛋白激酶——哺乳动物雷帕霉素复合物1mTORC1)——支持细胞生长。与该概念一致的是, Slc7a5转运氨基酸可调节多种细胞类型中的mTORC1活性。

来自美国克莱姆森大学的Aidan M. Sokolov所在团队最近研究发现Slc7a5敲低降低了mTORC1途径的活性,而Rheb的过量表达挽救了mTORC1途径的活性,证实了Slc7a5是颗粒细胞 mTOR通路活性、成熟和存活所必需的。这一发现可能有助于解释Slc7a5突变为何阻止正常的大脑发育和功能。Sokolov团队认为Slc7a5对大脑正常发育来说是必要的,并且Slc7a5的相关研究为了解氨基酸转运蛋白如何差异性调节神经系统中不同类型细胞和不同细胞过程提供了一种新思路。

 

文章在《中国神经再生研究(英文版)》杂志20211010期发表。

https://orcid.org//0000-0001-5985-9109 (David M. Feliciano)

Abstract: Membrane transport proteins are appreciated for their ability to transport molecules across biological membranes and have received a renewed focus for their role in nervous system disorders. One such group of transporters are members of the solute carrier (SLC) family. SLC transporters shuttle various molecules, including neurotransmitters, fatty acids, amino acids, and inorganic ions. As such, they play an integral role in supplying cells with essential resources. An example is that amino acids are transported by SLC family members. Slc7a5 is a SLC family member that transports essential amino acids important for neuronal development, as well as other biological molecules including thyroid hormones T3, T4, and L-Dopa. Slc7a5 forms a heterodimer with Slc3a2 that facilitates the subcellular distribution of Slc7a5. Amino acids including leucine, glutamine, and arginine support cell growth by activating the protein kinase, mammalian target of rapamycin complex 1 (mTORC1) (Liu et al., 2020). Consistent with this notion is that Slc7a5 transport of amino acids regulates mTORC1 activity in numerous cell types (Nicklin et al., 2009). A recent manuscript expands upon these findings to demonstrate that Slc7a5 plays a previously unrecognized and critical role in the regulation of mTORC1 activity and neuron development (Sokolov et al., 2020).