Possible Role for FMRP in Regulating Actin Cytoskeletal Dynamics

Castets et al. (2005) have reported a very exciting set of observations that may provide a link between FMRP and the actin dynamics likely to determine the shape of dendritic spines. In particular, they have demonstrated that FMRP appears to bind directly to the 5'-UTR of mRNA for phosphoser-ine/threonine phosphatase (PP2A; Zolnierowicz 2000), thus diminishing its translation. PP2A is a mediator of Rac1-coupled actin remodeling (Hall 1998; Janssens et al. 2005), which operates by shifting the balance from the inactive (phospho) to the active (dephospho) form of cofilin, an actin depolymerizing protein (Ambach et al. 2000; Meberg and Bamburg 2000; Samstag and Nebl 2003; Paavilainen et al. 2004). The principal finding of Castets et al. (2005) was that Rac1-induced actin remodeling was enhanced in cells that either lacked FMRP or possessed mutant forms of FMRP in which either the KH1 or KH2 domains were altered. These observations provide a possible basis for the altered dendritic spine morphology found in individuals with FXS.

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