Collapsin response mediator protein-2 is a calmodulin-binding protein.

Collapsin response mediator protein-2 is a calmodulin-binding protein.
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Collapsin 反应介导蛋白 2 是一种钙调蛋白结合蛋白。

DOI:
10.1007/s00018-008-8362-1
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发表时间:
2009
期刊:
Cellular and molecular life sciences : CMLS
影响因子:
--
通讯作者:
Wang,KKW
Wang,KKW
中科院分区:
--
文献类型:
--
作者:
Zhang,Z;Majava,V;Greffier,A;Hayes,RL;Kursula,P;Wang,KKW

文献摘要

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塌陷反应介质蛋白-2 (CRMP-2)在神经发育和再生过程中对轴突引导和神经突生长起着至关重要的作用。我们研究了钙调蛋白(CaM)与CRMP-2的相互作用,以及Ca2+/CaM结合如何调节CRMP-2的生物学功能。我们已经证明CRMP-2以Ca2+依赖的方式直接与CaM结合。CRMP-2的CaM结合位点位于折叠结构域的最后一个螺旋上,与此一致,合成了一个代表该螺旋与CaM结合的肽。此外,CaM结合抑制了CRMP-2的同四聚体组装,并减弱了calpain介导的CRMP-2蛋白水解。此外,CaM拮抗剂减少了HEK293细胞中由CRMP-2过表达诱导的过程的数量和长度。综上所述,我们的数据表明CRMP-2是一种新的CaM结合蛋白,CaM结合可能在调节CRMP-2功能中发挥重要作用。
Collapsin response mediator protein-2 (CRMP-2) plays a crucial role in axonal guidance and neurite outgrowth during neural development and regeneration. We have studied the interaction between calmodulin (CaM) and CRMP-2 and how Ca2+/CaM binding modulates the biological functions of CRMP-2. We have shown that CRMP-2 binds to CaM directly in a Ca2+-dependent manner. The CaM binding site of CRMP-2 is proposed to reside in the last helix of the folded domain, and in line with this, a synthesized peptide representing this helix bound to CaM. In addition, CaM binding inhibits a homotetrameric assembly of CRMP-2 and attenuates calpainmediated CRMP-2 proteolysis. Furthermore, a CaM antagonist reduces the number and length of process induced by CRMP-2 overexpression in HEK293 cells. Take together, our data suggest that CRMP-2 is a novel CaM-binding protein and that CaM binding may play an important role in regulating CRMP-2 functions.