The Role Of Myosin X In Axon Outgrowth

During the development of nervous system, axons of newborn neuron undergo a certain distance to their appropriate targets, form synaptic contacts and then establish the precise sophisticated network of the nervous system. Neuron's correct migration and the axon growth direction's precise guidance are fundamental to development of brain circuitry. However, the abnormal axon will cause the many kinds of nervous system diseases, such as congenital mental handicap, epilepsy, and so on. Therefore, it is more significant to research the molecular mechanism of axon growth for nervous system disease's treatment.MyosinⅩ(MyoⅩ), a vertebrate-specific member of myosin super-family, was discovered in inner ear by PCR in 1994. MyoⅩ, an actin-based motor protein, was detected in most tissues, such as kidney, liver, brain, and so on. MyoⅩlocalizes at the tips of filopodia, can undergo forward and reaward movement within filopodia, and promote filopodia formation and stabilization. It has been reported that MyoⅩexhibits dramatic developmental regulation in brain. In mouse cerebrum, full-length MyoⅩexhibit a peak of expression between postnatal days 5-15, with much lower expression levels in the adult.In this study, the cultured newborn hippocampal neurons was used as a model to study the roles that MyoⅩplay in regulating the outgrowth of axons and dendrites. When the cultured hippocampal neurons was immunolabeled for the axonal marker Tau1 or dendrite marker MAP2 at 5 days in vitro, MyoⅩwas expressed in the axon, dendrite and soma, co-localized with Tau1 in the axon and with MAP2 in the dendrites, respectively. Dissociated hippocampal neurons were transfected with MyoⅩ-siRNA expressional vector, after 72 h, the results showed that the length of axons was significantly shorter than that in the control neurons. However, transfection cultured neuron at DIV 2 with either scramble-siRNA or MyoⅩ-siRNA, and detected neuronal morphology after transfection 2 days. Although the length of axons was not significantly changed, the number of neurites on MyoⅩ-siRNA neurons was less than that on scramble-siRNA neuron. In addition, most neurons expressing MyoⅩ-siRNA no longer possessed a single long axon–like neurite, resulting in a loss of the characteristic neuronal polarity, even in the 90.5% cells did not display detectable tau1 labeling in any neurites of neuron expressing MyoⅩ-siRNA. So, reduction of endogeous MyoⅩcan cause axon growth defect in hippocampal neurons, hinder the establishment of neuronal polarity. In summary, MyoⅩplays an important role in regulating the outgrowth of axons and dendrites.