丝将质膜雕刻成细胞素来控制细胞间的通讯。

IF 8.3 1区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY EMBO Journal Pub Date : 2025-04-01 Epub Date: 2025-03-06 DOI:10.1038/s44318-025-00401-8
Basile Rambaud, Mathieu Joseph, Feng-Ching Tsai, Camille De Jamblinne, Regina Strakhova, Emmanuelle Del Guidice, Renata Sabelli, Matthew J Smith, Patricia Bassereau, David R Hipfner, Sébastien Carréno
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引用次数: 0

摘要

细胞素是一种信号丝状足,通过在细胞间形成突触来促进细胞间的远距离通讯。它们最初是在果蝇中发现的,用于在胚胎发生过程中运输形态因子,后来在哺乳动物细胞中被发现,并与致癌有关。尽管它们很重要,但控制细胞素生物发生的机制仍然难以捉摸。在这里,我们证明了丝氨酸/苏氨酸激酶通过促进细胞素的形成来驱动远程细胞增殖。这个功能依赖于Slik的螺旋结构域(SlikCCD),它直接将膜雕刻成小管。重要的是,Slik在细胞素的生物发生中起着相反的作用:它的膜雕刻活性促进细胞素的形成,但这被它的激酶活性抵消,激酶活性通过Moesin磷酸化增强肌动蛋白与质膜的关联。在体内,SlikCCD可增强翼盘上皮层细胞素的形成,从而促进相邻层细胞的增殖。最后,该功能依赖于STRIPAK复合物,该复合物通过调节丝与质膜的结合来控制细胞素的形成和远距离的增殖。我们的研究揭示了一个意想不到的结构作用的激酶雕刻膜,至关重要的细胞素介导的细胞增殖控制。
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Slik sculpts the plasma membrane into cytonemes to control cell-cell communication.

Cytonemes are signaling filopodia that facilitate long-range cell-cell communication by forming synapses between cells. Initially discovered in Drosophila for transporting morphogens during embryogenesis, they have since been identified in mammalian cells and implicated in carcinogenesis. Despite their importance, mechanisms controlling cytoneme biogenesis remain elusive. Here, we demonstrate that the Ser/Thr kinase Slik drives remote cell proliferation by promoting cytoneme formation. This function depends on the coiled-coil domain of Slik (SlikCCD), which directly sculpts membranes into tubules. Importantly, Slik plays opposing roles in cytoneme biogenesis: its membrane-sculpting activity promotes cytoneme formation, but this is counteracted by its kinase activity, which enhances actin association with the plasma membrane via Moesin phosphorylation. In vivo, SlikCCD enhances cytoneme formation in one epithelial layer of the wing disc to promote cell proliferation in an adjacent layer. Finally, this function relies on the STRIPAK complex, which controls cytoneme formation and governs proliferation at a distance by regulating Slik association with the plasma membrane. Our study unveils an unexpected structural role of a kinase in sculpting membranes, crucial for cytoneme-mediated control of cell proliferation.

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来源期刊
EMBO Journal
EMBO Journal 生物-生化与分子生物学
CiteScore
18.90
自引率
0.90%
发文量
246
审稿时长
1.5 months
期刊介绍: The EMBO Journal has stood as EMBO's flagship publication since its inception in 1982. Renowned for its international reputation in quality and originality, the journal spans all facets of molecular biology. It serves as a platform for papers elucidating original research of broad general interest in molecular and cell biology, with a distinct focus on molecular mechanisms and physiological relevance. With a commitment to promoting articles reporting novel findings of broad biological significance, The EMBO Journal stands as a key contributor to advancing the field of molecular biology.
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