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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Publication Details

Journal
The EMBO Journal
Published
2025-03-06
DOI
https://doi.org/10.1038/s44318-025-00401-8
Primary Topic
Cellular transport and secretion
Type
article
Field-Weighted Citation Impact
0.00

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article

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

Feng‐Ching Tsai, Mathieu Joseph, Sébastien Carreno, Regina Strakhova et al.
The EMBO Journal
Cellular transport and secretion
article

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

Feng‐Ching Tsai, Mathieu Joseph, Sébastien Carreno, Regina Strakhova, Basile Rambaud, Matthew James Smith, Camille De Jamblinne, Patricia Bassereau, David R. Hipfner, Emmanuelle Del Guidice, Renata Sabelli
article en

Abstract

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.

The EMBO JournalVol. 44(8)
Centre National de la Recherche Scientifique (FR), Université Paris Sciences et Lettres (FR), Sorbonne Université (FR), Institute for Research in Immunology and Cancer (CA), Montreal Clinical Research Institute (CA), Université de Montréal (CA), Institut Curie (FR)
Agence Nationale de la Recherche, Canada Research Chairs, Wallonie-Bruxelles International, Natural Sciences and Engineering Research Council of Canada, Fonds de recherche du Québec – Nature et technologies, Labex Immuno-Oncology, Institute of Cancer Research
Openalex Percentile: Top 95%
Cellular transport and secretion
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