Slik sculpts the plasma membrane into cytonemes to control cell-cell communication

被引:0
|
作者
Rambaud, Basile [1 ,2 ]
Joseph, Mathieu [2 ,3 ]
Tsai, Feng-Ching [4 ]
De Jamblinne, Camille [1 ,2 ]
Strakhova, Regina [1 ,2 ]
Del Guidice, Emmanuelle [1 ,2 ]
Sabelli, Renata [1 ,2 ]
Smith, Matthew J. [1 ,2 ,5 ]
Bassereau, Patricia [4 ]
Hipfner, David R. [2 ,3 ,6 ]
Carreno, Sebastien [1 ,2 ,5 ]
机构
[1] Univ Montreal, Inst Res Immunol & Canc IRIC, Montreal, PQ H3C 3J7, Canada
[2] Univ Montreal, Programmes Biol Mol, Montreal, PQ H3C 3J7, Canada
[3] Inst Rech Clin Montreal IRCM, Montreal, PQ H2W 1R7, Canada
[4] Sorbonne Univ, Univ PSL, Inst Curie, CNRS,UMR168,Phys Cells & Canc, F-75005 Paris, France
[5] Univ Montreal, Dept Pathol & Biol Cellulaire, Montreal, PQ H3C 3J7, Canada
[6] Univ Montreal, Dept Med, Montreal, PQ H3C 3J7, Canada
来源
EMBO JOURNAL | 2025年
基金
加拿大自然科学与工程研究理事会;
关键词
Slik Kinase; Cytoneme Biogenesis; Membrane Sculpting; STRIPAK Complex; ERM Protein; KINASE SLIK; STRUCTURAL BASIS; DROSOPHILA; MOESIN; HEDGEHOG; IRSP53; PROLIFERATION; GRADIENT; PLATFORM; RELEASE;
D O I
10.1038/s44318-025-00401-8
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页码:2186 / 2210
页数:25
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