LST1 promotes the assembly of a molecular machinery responsible for tunneling nanotube formation

TLDR

Intercellular communication is essential for multicellular development, and tunneling nanotubes (TNT) are a newly recognized widespread mechanism, though their molecular basis remains poorly understood. The study reports that the transmembrane protein LST1 induces functional nanotube formation and is required for endogenous nanotube generation. LST1 acts as a membrane scaffold that assembles a multimolecular complex controlling functional nanotube formation. LST1 recruits RalA to the plasma membrane, facilitates its interaction with the exocyst complex, and also brings in filamin, M‑Sec, myosin, and myoferlin, supporting a model for nanotube generation.

Abstract

Carefully orchestrated intercellular communication is an essential prerequisite for the development of multicellular organisms. In recent years, tunneling nanotubes (TNT) have emerged as a novel and widespread mechanism of cell-cell communication. However, the molecular basis of their formation is still poorly understood. In the present study we report that the transmembrane MHC class III protein LST1 induces the formation of functional nanotubes and is required for endogenous nanotube generation. Mechanistically, we found LST1 to induce nanotube formation by recruiting the small GTPase RalA to the plasma membrane and promoting its interaction with the exocyst complex. Furthermore, we determined LST1 to recruit the actin-crosslinking protein filamin to the plasma membrane and to interact with M-Sec, myosin and myoferlin. These results allow us to suggest a molecular model for nanotube generation. In this proposal LST1 functions as a membrane scaffold mediating the assembly of a multimolecular complex, which controls the formation of functional nanotubes.