Neurofibromatosis 2 Tumor Suppressor Protein, Merlin, in Cellular Signaling to Actin Cytoskeleton

摘要

Th gene encoding the NF2 tumor suppressor showed a strong similarity to a family of cytoskeleton-associated proteins and was named merlin (for moesin-ezrin-radixin-like protein). The critical question as to how the NF2 gene product, merlin, acts as a tumor suppressor largely remains unanswered because of the limited knowledge of the physiological function of merlin. Our studies reveal that merlin can bind to actin directly and isoform 2 of merlin which does not show self association bind actin more efficiently than isoform 1. We have also observed that merlin/ERM binding partner NHE-RF interacts with the PDGF receptor. Actin reorganization is an integral part of signal transduction pathways, and many of the signaling molecules interact with the actin cytoskeleton. In particular, the Rho family member Rac when activated by PDGF induces membrane ruffling. Our observation that the translocation of endogenous merlin to membrane ruffles is stimulated by serum or PDGF, and the interaction of NHE-RF with the PDGF receptor strongly suggests a role for merlin in Rac mediated cellular signaling to actin cytoskeleton which will be the focus of our study in the next two year period.