The activated neurotrophin and receptor complex can promote neuron growth through regulating gene expression, only when the complex has been transported to neuron soma from the terminal of axon or presynapse Figure 5. It appeared that neurotrophin and its receptor are firstly endocytosed into cells and then transported to the cell nucleus periphery by interacting with cytoplasmic dynein in some unknown manner, which allows extracellular signals to be sent to the cell nucleus [ 58 ].
NGF binding to TrkA extracellular domain leads to a conformation change in its cytoplasmic domain and autophosphorylation its tyrosine residues, which enhance TrkA kinase activity [ 59 ]. BDNF has been demonstrated to regulate dendritic arborization and outgrowth during neuronal development [ 63 ]. The signaling endosomes then associate with dynein motor to undergo axonal retrograde transport to cell body to induce nuclear signal pathway [ 66 ].
Neurotransmission is the most important function of neuron system, a process of systematic communication between two neuronal cells. During the transmission, the neurotransmitters in the presynapse are released into the synaptic cleft and bind to the specific receptors on the postsynapse membrane. In presynapse, the synaptic vesicles containing neurotransmitters need to undergo a long axonal anterograde transport to reach the presynapse [ 68 ].
Additionally, myosin V has also been shown to associate with synaptic vesicles. In hippocampal neurons, myosin Va associates with the postsynaptic density PSD through directly interacting with guanylate kinase domain-associated protein GKAP , which binds to PSD [ 72 , 73 ]. In postsynapse Figure 5 , the receptors need to be transported to and from the postsynaptic membrane [ 76 ]. Myosin VI has been reported to interact with alpha-aminohydroxymethylisoxazolepropionic acid receptor AMPAR , a glutamate receptor, through binding directly to synapse-associated protein 97 SAP97 [ 77 ].
It implies that the motors can recognize the cargo through specific interactions with adaptor proteins. Also, the different kinds of motors may act in a coherent manner during the cargo transportation process [ 79 , 80 ]. During this process, muskelin acts as the interconnector between actin-based retrograde trafficking and microtubule-based retrograde trafficking of GABAR. Some cytoskeleton motors, including myosin Ic, myosin III and myosin IX, play other roles as mechanoforce sensor, tether and signaling regulator.
Myosin Ic directly binds to cell membranes through the C-terminal pleckstrin homology PH motif, which allows it to crosslink the membranes and actin filaments and transduce the mechanical force from tail-binding membranes to head-binding filaments in inner ear stereocilia [ 83 ].
A recent structural study showed that myosin Ic undergoes CaM-mediated conformational transformation upon mechanical force transduction [ 84 ]. Myosin III was also found to stimulate the elongation of stereocilia in hair cells through tethering and activating Espin1 at the tips of stereocilia, the plus ends of actin filaments [ 85 ].
Gene mutations in encoding these proteins can lead to hear loss disease [ 86 , 87 ]. In general, these diverse role manifests an integrated and complex function of myosin in cellular processes. We have summarized and discussed the roles of cytoskeleton motors during neuronal development and transmission function.
However, the structural basis for intracellular trafficking and regulations are not yet fully understood. Study on cytoskeleton motors' trafficking in neuron can help us to understand the cause of a variety of brain and nervous disorders. Although much progress has been made in past decades, structural study of neuronal-intracellular trafficking is still an attractive topic, especially in light of recent advance in macromolecule complex structure solvation technology, such as single particle cryo-EM [ 92 ].
To gain further mechanistic insights, we envisage that the following three aspects of intracellular trafficking pertaining to cytoskeleton motors deserve special attentions:. R FDCT project reference no. JCYJ to Z. Odronitz F, Kollmar M. Drawing the tree of eukaryotic life based on the analysis of 2, manually annotated myosins from species. Genome Biol. New insights into myosin evolution and classification. Axonal myosins. J Neurocytol.
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