Abstract
Neuronal polarization and growth are developmental processes that occur during neuronal cell differentiation. The molecular signaling mechanisms involved in these events in in vivo mammalian brain remain unclear. Also, cellular events of the neuronal polarization process within a given neuron are thought to be constituted of many independent intracellular signal transduction pathways (the “tug-of-war” model). However, in vivo results suggest that such pathways should be cooperative with one another among a given group of neurons in a region of the brain. Lipid rafts, specific membrane domains with low fluidity, are candidates for the hotspots of such intracellular signaling. Among the signals reported to be involved in polarization, a number are thought to be present or translocated to the lipid rafts in response to extracellular signals. As part of our analysis, we discuss how such novel molecular mechanisms are combined for effective regulation of neuronal polarization and growth, focusing on the significance of the lipid rafts, including results based on recently introduced methods.
Highlights
Brain development in mammals is believed to involve six steps, including: (1) segmentation of brain regions; (2) neuronal differentiation from neural stem cells; (3) neuronal migration to the appropriate locations; (4) neuronal polarity determination and axon growth as directed by guidance molecules; (5) synaptogenesis; and (6) removal of excess synapses (Sanes et al, 2019)
Among the many proteins involved in neuronal polarization (Takano et al, 2019), more than 10 species that are present upstream of the signaling have been reported to be present in lipid rafts or to be translocated to lipid rafts when the corresponding signals are activated (Table 1). These results suggest that those molecules are likely to function in polarization signaling as the concentrated forms in lipid rafts
Inhibition of Glycoprotein M6a (GPM6a) palmitoylation abolished LN-dependent determination, indicating that the trafficking of this protein to lipid rafts is essential to GPM6a’s mechanism of action (Honda et al, 2017a,b), even though GPM6a, being an intrinsic membrane protein already localizes to the plasma membrane (Ito et al, 2018)
Summary
Brain development in mammals is believed to involve six steps, including: (1) segmentation of brain regions; (2) neuronal differentiation from neural stem cells; (3) neuronal migration to the appropriate locations; (4) neuronal polarity determination and axon growth as directed by guidance molecules; (5) synaptogenesis; and (6) removal of excess synapses (Sanes et al, 2019). Inhibition of GPM6a palmitoylation abolished LN-dependent determination, indicating that the trafficking of this protein to lipid rafts is essential to GPM6a’s mechanism of action (Honda et al, 2017a,b), even though GPM6a, being an intrinsic membrane protein already localizes to the plasma membrane (Ito et al, 2018).
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