Calpain-mediated vimentin cleavage occurs upstream of MT1-MMP membrane translocation to facilitate endothelial sprout initiation.
Calpain-mediated vimentin cleavage occurs upstream of MT1-MMP membrane translocation to facilitate endothelial sprout initiation.
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DOI：
10.1007/s10456-012-9262-4
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发表时间：
2012-06
期刊：
影响因子：
9.8
通讯作者：
Bayless, Kayla J.
中科院分区：
文献类型：
--
作者：
Kwak, Hyeong-Il;Kang, Hojin;Dave, Jui M.;Mendoza, E. Adriana;Su, Shih-Chi;Maxwell, Steve A.;Bayless, Kayla J.
内皮细胞通常排列在脉管系统中并保持静止状态。然而，在适当的提示下，这些细胞可以被快速刺激进行形态发生并启动新血管的形成。这项研究报道了一种启动血管生成芽形成的新机制，该机制涉及内皮细胞中主要的中间丝蛋白波形蛋白。初步研究证实，1-磷酸鞘氨醇 (S1P) 和生长因子 (GF) 诱导的内皮细胞侵袭需要波形蛋白，并且波形蛋白在侵袭过程中被钙蛋白酶裂解。钙蛋白酶主要由 GF 激活，是发芽起始所必需的。由于其他人报道膜 1 型基质金属蛋白酶 (MT1-MMP) 是内皮出芽反应所必需的，因此我们测试了波形蛋白和钙蛋白酶是否在 MT1-MMP 上游发挥作用。钙蛋白酶和波形蛋白都是 MT1-MMP 膜易位成功所必需的，而受 S1P 刺激。此外，波形蛋白与 MT1-MMP 复合的方式需要 MT1-MMP 的胞质结构域和钙蛋白酶激活，从而增加了内皮细胞中波形蛋白的可溶性池。总而言之，这些数据表明促血管生成信号汇聚以激活钙蛋白酶依赖性波形蛋白裂解并增加波形蛋白溶解度，其在上游发挥作用以促进 MT1-MMP 膜易位，从而导致三维胶原基质中成功形成内皮芽。这些发现有助于解释为什么 S1P 和 GF 可以协同刺激 3D 胶原蛋白基质中的旺盛发芽。本文的在线版本 (doi:10.1007/s10456-012-9262-4) 包含补充材料，可供授权用户使用。
Endothelial cells normally line the vasculature and remain quiescent. However, these cells can be rapidly stimulated to undergo morphogenesis and initiate new blood vessel formation given the proper cues. This study reports a new mechanism for initiating angiogenic sprout formation that involves vimentin, the major intermediate filament protein in endothelial cells. Initial studies confirmed vimentin was required for sphingosine 1-phosphate (S1P)- and growth factor (GF)-induced endothelial cell invasion, and vimentin was cleaved by calpains during invasion. Calpains were predominantly activated by GF and were required for sprout initiation. Because others have reported membrane type 1-matrix metalloproteinase (MT1-MMP) is required for endothelial sprouting responses, we tested whether vimentin and calpain acted upstream of MT1-MMP. Both calpain and vimentin were required for successful MT1-MMP membrane translocation, which was stimulated by S1P. In addition, vimentin complexed with MT1-MMP in a manner that required both the cytoplasmic domain of MT1-MMP and calpain activation, which increased the soluble pool of vimentin in endothelial cells. Altogether, these data indicate that pro-angiogenic signals converge to activate calpain-dependent vimentin cleavage and increase vimentin solubility, which act upstream to facilitate MT1-MMP membrane translocation, resulting in successful endothelial sprout formation in three-dimensional collagen matrices. These findings help explain why S1P and GF synergize to stimulate robust sprouting in 3D collagen matrices. The online version of this article (doi:10.1007/s10456-012-9262-4) contains supplementary material, which is available to authorized users.
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影响因子：
19
作者：
Helfand, BT;Chou, YH;Goldman, RD
通讯作者：
Goldman, RD
影响因子：
64.5
作者：
Hiraoka, N;Allen, E;Weiss, SJ
通讯作者：
Weiss, SJ
DOI：
10.1083/jcb.200703185
发表时间：
2007-11-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Flevaris P;Stojanovic A;Gong H;Chishti A;Welch E;Du X
通讯作者：
Du X
DOI：
10.1083/jcb.149.6.1309
发表时间：
2000-06-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hotary K;Allen E;Punturieri A;Yana I;Weiss SJ
通讯作者：
Weiss SJ
DOI：
10.1083/jcb.200708048
发表时间：
2008-03-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cortesio CL;Chan KT;Perrin BJ;Burton NO;Zhang S;Zhang ZY;Huttenlocher A
通讯作者：
Huttenlocher A