Myosin X and its motorless isoform differentially modulate dendritic spine development by regulating trafficking and retention of vasodilator-stimulated phosphoprotein.
Myosin X (Myo10) is an unconventional myosin with two known isoforms: full-length (FL)-Myo10 that has motor activity, and a recently identified brain-expressed isoform, headless (Hdl)-Myo10, which lacks most of the motor domain. FL-Myo10 is involved in the regulation of filopodia formation in non-neuronal cells; however, the biological function of Hdl-Myo10 remains largely unknown. Here, we show that FL- and Hdl-Myo10 have important, but distinct, roles in the development of dendritic spines and synapses in hippocampal neurons. FL-Myo10 induces formation of dendritic filopodia and modulates filopodia dynamics by trafficking the actin-binding protein vasodilator-stimulated phosphoprotein (VASP) to the tips of filopodia. By contrast, Hdl-Myo10 acts on dendritic spines to enhance spine and synaptic density as well as spine head expansion by increasing the retention of VASP in spines. Thus, this study demonstrates a novel biological function for Hdl-Myo10 and an important new role for both Myo10 isoforms in the development of dendritic spines and synapses.
Department of Biological Sciences and Vanderbilt Kennedy Center for Research on Human Development, Vanderbilt University, Nashville, Tennessee 37235, USA.
Wan-Hsin
WH
Lin
Joshua T
JT
Hurley
Alexander N
AN
Raines
Richard E
RE
Cheney
Donna J
DJ
Webb
D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology; D049229:Dendritic Spines / Q000378:metabolism* / Q000502:physiology; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D009218:Myosins / Q000235:genetics / Q000378:metabolism*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D021381:Protein Transport; D011554:Pseudopodia / Q000378:metabolism; D051381:Rats; D013569:Synapses / Q000378:metabolism; D014162:Transfection; D000098662:Vasodilator-Stimulated Phosphoprotein
D015815:Cell Adhesion Molecules; C498718:MYO10 protein, human; D008840:Microfilament Proteins; D010750:Phosphoproteins; D020033:Protein Isoforms; D000098662:Vasodilator-Stimulated Phosphoprotein; D009218:Myosins
Dendritic spine; Filopodia; Hippocampal neuron; Myosin; Synapse