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.
Slik sculpts the plasma membrane into cytonemes to control cell-cell communication.
Slik 将质膜塑造成细胞丝,以控制细胞间的通讯
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作者:Rambaud Basile, Joseph Mathieu, Tsai Feng-Ching, De Jamblinne Camille, Strakhova Regina, Del Guidice Emmanuelle, Sabelli Renata, Smith Matthew J, Bassereau Patricia, Hipfner David R, Carréno Sébastien
| 期刊: | EMBO Journal | 影响因子: | 8.300 |
| 时间: | 2025 | 起止号: | 2025 Apr;44(8):2186-2210 |
| doi: | 10.1038/s44318-025-00401-8 | 研究方向: | 细胞生物学 |
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