1. ¹Department of Pathology, Biomedicum Helsinki, University of Helsinki, Helsinki, Finland
2. ²Department of Pathology, University of Turku and Turku University Central Hospital, Turku, Finland

Correspondence: M Laulajainen, Department of Pathology, Biomedicum Helsinki, Helsinki University, Haartmaninkatu 8, PL 63, Helsinki, Helsinki 14, Finland. E-mail: minja.laulajainen@helsinki.fi

³These authors have contributed equally to this work.

Received 28 August 2007; Revised 13 November 2007; Accepted 15 November 2007; Published online 10 December 2007.

Abstract

Mutations in the neurofibromatosis 2 tumor suppressor gene (NF2) encoding merlin (moesin–ezrin–radixin like-protein) induce tumors of the nervous system. Merlin localizes to the cell membrane where it links the actin cytoskeleton to membrane proteins. Cell proliferation is regulated by merlin in many cell types, but merlin's tumor suppressor function still remains unclear. Phosphorylation has been suggested to regulate merlin's activity. The C-terminal serine 518 is phosphorylated both by p21-activated kinases (PAKs) and protein kinase A (PKA). In this work, we identify a novel PKA phosphorylation site, serine 10, in the N terminus of merlin. We show that a non-phosphorylatable form of serine 10 (S10A) affects cellular morphology. Regulation of this site also influences actin cytoskeleton organization and dynamics in vivo, as merlin S10A reduces the amount of cellular F-actin and merlin S10D stabilizes F-actin filaments. By using a wound-healing assay and live cell imaging, we demonstrate that dephosphorylation of serine 10 leads to defects in migration, possibly through altered ability of the cells to form lamellipodia. This study suggests a role for merlin in mediating PKA-induced changes of the actin cytoskeleton.