title: Myosin Va is required for the transport of fragile X mental retardation protein (FMRP) granules.
abstract: BACKGROUND
  Fragile X mental retardation protein (FMRP) is a selective RNA binding protein that functions as a translational inhibitor. It also plays a role in directing the transport of a subset of mRNAs to their site of translation and several recent reports have implicated microtubule motor proteins in the transport of FMRP-messenger ribonucleoprotein (mRNP) granules in neurons. Earlier work reported the association of the actin-based motor protein myosin Va with FMRP granules.
  
  
  RESULTS
  Here, we follow up on this finding and confirm that myosin Va does in fact associate with FMRP and is required for its correct intracellular localisation. FMRP is concentrated in the perinuclear region of myosin Va-null mouse melanoma cells which contrasts starkly with the evenly distributed punctate pattern observed in wild-type cells. Similarly, overexpression of a dominant-negative mutant of myosin Va results in the accumulation of FMRP in large aggregate-like structures. FRAP experiments demonstrate that FMRP is largely immobile in the absence of myosin Va.
  
  
  CONCLUSIONS
  Combining these data, we propose a model in which myosin Va and kinesin play key roles in the assembly and subsequent transport of FMRP granules along microtubules to the periphery of the cell. Myosin Va captures the complex onto peripheral actin structures and mediates the local delivery of the FMRP granule to the site of mRNA translation.
authors.affiliation: Molecular Cell Biology Laboratory, School of Biochemistry and Cell Biology, Biosciences Institute, University College Cork, Cork, Ireland.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Lindsay
authors.forename: Mary W
authors.initials: MW
authors.lastname: McCaffrey
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D003594:Cytoplasmic Granules / Q000235:genetics / Q000378:metabolism*; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D016547:Kinesins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008870:Microtubules / Q000378:metabolism; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism*; D024701:Myosin Type V / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1; D016547:Kinesins; D018995:Myosin Heavy Chains; D024701:Myosin Type V; C513082:Myo5a protein, mouse
keywords: Actin; FRAP; Fragile X mental retardation protein; Microtubules; Myosin Va; mRNA transport