The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin
(ERM) protein family are involved in numerous key cellular processes in the cytoplasm.
In the last decades, ERM proteins, like actin and other cytoskeletal components, have
also been shown to be functional components of the nucleus; however, the molecular
mechanism behind their nuclear activities remained unclear. Therefore, our primary
aim was to identify the nuclear protein interactome of the single Drosophila ERM protein,
Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through
direct binding to its Med15 subunit, and the presence of Moesin at the regulatory
regions of the Hsp70Ab heat shock gene was found to be Med15-dependent. Both Moesin
and Med15 bind to heat shock factor (Hsf), and they are required for proper Hsp gene
expression under physiological conditions. Moreover, we confirmed that Moesin, Med15
and Hsf are able to bind the monomeric form of actin and together they form a complex
in the nucleus. These results elucidate a mechanism by which ERMs function within
the nucleus. Finally, we present the direct interaction of the human orthologues of
Drosophila Moesin and Med15, which highlights the evolutionary significance of our
finding.
