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

## TL;DR

This study reveals how the kinase Slik shapes cell membranes into cytonemes, which help cells communicate and grow at a distance.

## Contribution

The novel contribution is identifying Slik's dual role in membrane sculpting and cytoneme formation, revealing a new mechanism for cell-cell communication.

## Key findings

- Slik's coiled-coil domain sculpts membranes into tubules to form cytonemes.
- Slik's kinase activity counteracts cytoneme formation by phosphorylating Moesin.
- STRIPAK regulates Slik's membrane association to control cytoneme formation and cell proliferation.

## Abstract

Cytonemes are specialized cellular protrusions that mediate cell–cell communication at a distance. This study identifies Slik as a unique Ser/Thr kinase that is essential for cytoneme biogenesis, with dual roles in membrane sculpting and regulating cortical stiffness.

Slik balances cytoneme biogenesis by promoting membrane tubulation through its coiled-coil domain and counteracting their formation via Moesin activation through its kinase domain.Slik-dependent cytonemes promote cell proliferation at a distance.STRIPAK controls cytoneme formation by regulating Slik association with the plasma membrane.

Slik balances cytoneme biogenesis by promoting membrane tubulation through its coiled-coil domain and counteracting their formation via Moesin activation through its kinase domain.

Slik-dependent cytonemes promote cell proliferation at a distance.

STRIPAK controls cytoneme formation by regulating Slik association with the plasma membrane.

The Ser/Thr kinase Slik promotes membrane tubulation through its coiled-coil domain and counteracts it via Moesin activation through its kinase domain.

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.