Myosin-Va facilitates the accumulation of mRNA/protein complex in dendritic spines.
mRNA localization has an essential role in localizing cytoplasmic determinants, controlling the direction of protein secretion, and allowing the local control of protein synthesis in neurons. In neuronal dendrites, the localization and translocation of mRNA is considered as one of the molecular bases of synaptic plasticity. Recent imaging and functional studies revealed that several RNA-binding proteins form a large messenger ribonucleoprotein (mRNP) complex that is involved in transport and translation of mRNA in dendrites. However, the mechanism of mRNA translocation into dendritic spines is unknown. Here, we show that an actin-based motor, myosin-Va, plays a significant role in mRNP transport in neuronal dendrites and spines. Myosin-Va was Ca2+-dependently associated with TLS, an RNA-binding protein, and its target RNA Nd1-L, an actin stabilizer. A dominant-negative mutant or RNAi of myosin-Va in neurons suppressed TLS accumulation in spines and further impaired TLS dynamics upon activation of mGluRs. The TLS translocation into spines was impeded also in neurons prepared from myosin-Va-null dilute-lethal (dl) mice, which exhibit neurological defects. Our results demonstrate that myosin-Va facilitates the transport of TLS-containing mRNP complexes in spines and may function in synaptic plasticity through Ca2+ signaling.
Yoshimura
Atsushi
A
Osaka Bioscience Institute, Suita, Osaka 565-0874, Japan.
Fujii
Ritsuko
R
Watanabe
Yasuhito
Y
Okabe
Shigeo
S
Fukui
Kenji
K
Takumi
Toru
T
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D049229:Dendritic Spines / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D018995:Myosin Heavy Chains / Q000502:physiology*; D024701:Myosin Type V / Q000502:physiology*; D021381:Protein Transport; D011506:Proteins / Q000235:genetics; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism*; D034702:RNA-Binding Protein FUS / Q000378:metabolism; D012261:Ribonucleoproteins / Q000378:metabolism*
D047908:Intracellular Signaling Peptides and Proteins; C513082:Myo5a protein, mouse; C432129:Nd1 protein, mouse; D011506:Proteins; D012333:RNA, Messenger; D034702:RNA-Binding Protein FUS; D012261:Ribonucleoproteins; D024701:Myosin Type V; D018995:Myosin Heavy Chains; D002118:Calcium