Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends.
Tubulin tyrosination is a major factor affecting the recruitment of CAP-Gly proteins at microtubule plus ends.
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DOI：
10.1083/jcb.200512058
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发表时间：
2006-09-11
期刊：
影响因子：
--
通讯作者：
Job D
中科院分区：
文献类型：
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作者：
Peris L;Thery M;Fauré J;Saoudi Y;Lafanechère L;Chilton JK;Gordon-Weeks P;Galjart N;Bornens M;Wordeman L;Wehland J;Andrieux A;Job D
微管蛋白酪氨酸连接酶（TTL）是在微管蛋白酪氨酸化循环中催化C-末端酪氨酸残基添加到α-微管蛋白的酶，参与肿瘤进展并在神经元组织中起重要作用。我们发现，在哺乳动物成纤维细胞，细胞质连接蛋白（CLIP）170和其他微管加端跟踪蛋白，包括一个cytokerion相关的蛋白质甘氨酸丰富（CAP-Gly）微管结合域，如CLIP-115和p150胶合，本地化的酪氨酸化微管的末端，但不去酪氨酸化微管的末端。在体外，CLIP-170和p150 Glued的头部结构域与酪氨酸化微管的结合比与去酪氨酸化聚合物的结合更有效。在TTL无效的成纤维细胞，微管蛋白酪氨酸和CAP-Gly蛋白的错误定位与缺陷的纺锤体定位在有丝分裂和细胞形态在间期。这些结果表明，微管蛋白酪氨酸调节微管与CAP-Gly微管加末端跟踪蛋白的相互作用，并提供TTL参与肿瘤进展和神经元组织的解释。
Tubulin-tyrosine ligase (TTL), the enzyme that catalyzes the addition of a C-terminal tyrosine residue to α-tubulin in the tubulin tyrosination cycle, is involved in tumor progression and has a vital role in neuronal organization. We show that in mammalian fibroblasts, cytoplasmic linker protein (CLIP) 170 and other microtubule plus-end tracking proteins comprising a cytoskeleton-associated protein glycine-rich (CAP-Gly) microtubule binding domain such as CLIP-115 and p150 Glued, localize to the ends of tyrosinated microtubules but not to the ends of detyrosinated microtubules. In vitro, the head domains of CLIP-170 and of p150 Glued bind more efficiently to tyrosinated microtubules than to detyrosinated polymers. In TTL-null fibroblasts, tubulin detyrosination and CAP-Gly protein mislocalization correlate with defects in both spindle positioning during mitosis and cell morphology during interphase. These results indicate that tubulin tyrosination regulates microtubule interactions with CAP-Gly microtubule plus-end tracking proteins and provide explanations for the involvement of TTL in tumor progression and in neuronal organization.