VSTM2L is a novel secreted antagonist of the neuroprotective peptide Humanin
VSTM2L is a novel secreted antagonist of the neuroprotective peptide Humanin
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DOI：
10.1096/fj.10-163535
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发表时间：
2011-06-01
期刊：
影响因子：
4.8
通讯作者：
Caricasole, Andrea
中科院分区：
文献类型：
--
作者：
Rossini, Lara;Hashimoto, Yuichi;Caricasole, Andrea
Humanin（HN）是一种24-残基肽，其在体外对一系列细胞毒性和神经毒性损伤显示保护活性，并且在实验模型中介导阿尔茨海默病（AD）相关记忆障碍的体内改善。已发表的证据表明，HN发挥其细胞和神经保护活性的机制可能包括其分泌和结合膜相关受体。在这里，我们描述了一种新的HN神经保护活性的调节剂，V-set和跨膜结构域包含2样（VSTM 2L），以前称为C20 orf 102的鉴定。VSTM 2L在酵母和哺乳动物细胞中与HN相互作用，在培养细胞中分泌，存在于血清中，并在中枢神经系统中选择性表达。VSTM 2L与HN共定位于不同的脑区域以及原代培养的神经元中，其中它在神经元活力的调节中起作用。当在HN神经保护生物测定中测试时，VSTM 2L充当HN神经保护活性的强拮抗剂。总之，VSTM 2L是HN分泌型拮抗剂的第一个例子，可能在调节HN生物功能中发挥作用-Rossini，L.，桥本，Y.，铃木，H.，栗田，M.，Gianfriddo，M.，Scali，C.，龙卡拉蒂河Franceschini，D.，Pollio，G.，特拉巴尔齐尼湖特斯塔彭湾C.的方法，Matsuoka，M.，Caricasole，A. VSTM 2L是一种新型的神经保护肽Humanin的分泌型拮抗剂。FASEB J. 25，1983-2000（2011）。www.fasebj.org
Humanin (HN) is a 24-residue peptide displaying a protective activity in vitro against a range of cytotoxic and neurotoxic insults, as well as mediating in vivo amelioration of Alzheimer disease (AD)-related memory impairment in experimental models. Published evidence suggests that the mechanisms through which HN exerts its cyto- and neuroprotective activity may include its secretion and binding to membrane-associated receptors. Here, we describe the identification of a new modulator of HN neuroprotective activity, V-set and transmembrane domain containing 2 like (VSTM2L), previously known as C20orf102. VSTM2L interacts with HN in both yeast and mammalian cells, is secreted in cultured cells, is present in serum, and is selectively expressed in the central nervous system. VSTM2L colocalizes with HN in distinct brain areas as well as in primary cultured neurons, where it plays a role in the modulation of neuronal viability. When tested in HN neuroprotection bioassays, VSTM2L acts as a strong antagonist of HN neuroprotective activity. In summary, VSTM2L is the first example of a secreted antagonist of HN and may play a role in the modulation of HN biological functions-Rossini, L., Hashimoto, Y., Suzuki, H., Kurita, M., Gianfriddo, M., Scali, C., Roncarati, R., Franceschini, D., Pollio, G., Trabalzini, L., Terstappen, G. C., Matsuoka, M., Caricasole, A. VSTM2L is a novel secreted antagonist of the neuroprotective peptide Humanin. FASEB J. 25, 1983-2000 (2011). www.fasebj.org