Schiller, Christian; Diakopoulos, Kalliope N.; Rohwedder, Ina; Kremmer, Elisabeth; Toerne, Christine von; Ueffing, Marius; Weidle, Ulrich H.; Ohno, Hiroshi; Weiss, Elisabeth H.
(13. Dezember 2012):
LST1 promotes the assembly of a molecular machinery responsible for tunneling nanotube formation.
In: Journal of Cell Science
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