The cell adhesion molecule transmembrane and immunoglobulin (Ig) domain containing1 (TMIGD1) is a novel tumor suppressor that plays important roles in regulating cell–cell adhesion, cell proliferation and cell cycle. However, the mechanisms of TMIGD1 signaling are not yet fully elucidated. TMIGD1 binds to the ERM family proteins moesin and ezrin, and an evolutionarily conserved RRKK motif on the carboxyl terminus of TMIGD1 mediates the interaction of TMIGD1 with the N-terminal ERM domains of moesin and ezrin. TMIGD1 governs the apical localization of moesin and ezrin, as the loss of TMIGD1 in mice altered apical localization of moesin and ezrin in epithelial cells. In cell culture, TMIGD1 inhibited moesin-induced filopodia-like protrusions and cell migration. More importantly, TMIGD1 stimulated the Lysine (K40) acetylation of α-tubulin and promoted mitotic spindle organization and CRISPR/Cas9-mediated knockout of moesin impaired the TMIGD1-mediated acetylation of α-tubulin and filamentous (F)-actin organization. TMIGD1 binds to moesin and ezrin, and regulates their cellular localization. Moesin plays critical roles in TMIGD1-dependent acetylation of α-tubulin, mitotic spindle organization and cell migration. Our findings offer a molecular framework for understanding the complex functional interplay between TMIGD1 and the ERM family proteins in the regulation of cell adhesion and mitotic spindle assembly, and have wide-ranging implications in physiological and pathological processes such as cancer progression.

中文翻译：

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细胞粘附分子 TMIGD1 与 moesin 结合并调节微管蛋白乙酰化和细胞迁移

细胞粘附分子跨膜和免疫球蛋白 (Ig) 结构域包含 1 (TMIGD1) 是一种新型肿瘤抑制因子，在调节细胞间粘附、细胞增殖和细胞周期中起重要作用。然而，TMIGD1 信号的机制尚未完全阐明。TMIGD1 与 ERM 家族蛋白 moesin 和 ezrin 结合，并且 TMIGD1 羧基末端的进化上保守的 RRKK 基序介导 TMIGD1 与 moesin 和 ezrin 的 N 端 ERM 结构域的相互作用。TMIGD1 控制 moesin 和 ezrin 的顶端定位，因为小鼠中 TMIGD1 的缺失改变了上皮细胞中 moesin 和 ezrin 的顶端定位。在细胞培养中，TMIGD1 抑制 moesin 诱导的丝状伪足样突起和细胞迁移。更重要的是，TMIGD1 刺激 α-微管蛋白的赖氨酸 (K40) 乙酰化并促进有丝分裂纺锤体组织和 CRISPR/Cas9 介导的 moesin 敲除损害了 TMIGD1 介导的 α-微管蛋白和丝状 (F)-肌动蛋白组织的乙酰化。TMIGD1 与 moesin 和 ezrin 结合，并调节它们的细胞定位。Moesin 在 α-微管蛋白的 TMIGD1 依赖性乙酰化、有丝分裂纺锤体组织和细胞迁移中起着关键作用。我们的研究结果为理解 TMIGD1 和 ERM 家族蛋白在调节细胞粘附和有丝分裂纺锤体组装方面的复杂功能相互作用提供了一个分子框架，并且在生理和病理过程（如癌症进展）中具有广泛的意义。