Myosin X regulates neuronal radial migration through interacting with N-cadherin

Abstract

Proper brain function depends on correct neuronal migration during development, which is known to be regulated by cytoskeletal dynamics and cell-cell adhesion. Myosin X (Myo10), an uncharacteristic member of the myosin family, is an important regulator of cytoskeleton that modulates cell motilities in many different cellular contexts. We previously reported that Myo10 was required for neuronal migration in the developing cerebral cortex, but the underlying mechanism was still largely unknown. Here, we found that knockdown of Myo10 expression disturbed the adherence of migrating neurons to radial glial fibers through abolishing surface Neuronal cadherin (N-cadherin) expression, thereby impaired neuronal migration in the developmental cortex. Next, we found Myo10 interacted with N-cadherin cellular domain through its FERM domain. Furthermore, we found knockdown of Myo10 disrupted N-cadherin subcellular distribution and led to localization of N-cadherin into Golgi apparatus and endosomal sorting vesicle. Taking together, these results reveal a novel mechanism of Myo10 interacting with N-cadherin and regulating its cell-surface expression, which is required for neuronal adhesion and migration.

Myosin X interaction with KIF13B, a crucial pathway for Netrin-1-induced axonal development

“…Accordingly, axons in control neurons crossed the midline as early as P3, while axons in MyoX-KD neurons failed to do that (Figure 1-Figure Supplement 1C and 1D). In addition, neuronal migration appeared to be impaired (Figure 1E and G), as reported previously using RNA interference technology (Lai et al, 2015). Given that MyoX KO neurons exhibited normal axonal length and midline crossing at P7, these results suggest a delayed initial axonal outgrowth.…”

F-actin dynamics transform filopodial bridges into intercellular nanotubes capable of distant cell communication

“…2e, Supplementary Movie 4), in which N-cadherin molecules are supposed to be transported in the anterograde direction. We suspect that myosin X, which is required for filopodium formation and extension, can deliver N-cadherin to the tip of the filopodium, as found in neuronal cells [49][50][51] , in contrast to the retraction of the filopodium during the transition of FBs. Since we did not observe the significant breakage of INTs once they were connected to the paired cell body, even under Ca 2+ depleted conditions ( Supplementary Fig.…”

MyTH4-FERM myosins in the assembly and maintenance of actin-based protrusions

“…These cargoes have been shown to differentially regulate Myo10 activity and induction of filopodia formation, with DCC enhancing basal filopodia elongation and neogenin promoting dorsal filopodia growth [45]. VE-cadherin and N-cadherin are Myo10 cargoes that function in the formation of early endothelial cell-cell contacts and neuronal radial migration, respectively [46,47]. Myo10 also plays a role in endothelial cell migration by transporting BMP6 receptor ALK6 and inducing filopodia formation in a BMP-dependent manner [48].…”