Neurofilament Transport Is Dependent on Actin and Myosin

Abstract

Real-time analyses have revealed that some newly synthesized neurofilament (NF) subunits translocate into and along axonal neurites by moving along the inner plasma membrane surface, suggesting that they may translocate against the submembrane actin cortex. We therefore examined whether or not NF axonal transport was dependent on actin and myosin. Perturbation of filamentous actin in NB2a/d1 cells with cytochalasin B inhibited translocation of subunits into axonal neurites and inhibited bidirectional translocation of NF subunits within neurites. Intravitreal injection of cytochalasin B inhibited NF axonal transport in optic axons in a dose-response manner. NF subunits were coprecipitated from NB2a/d1 cells by an anti-myosin antibody, and myosin colocalized with NFs in immunofluorescent analyses. The myosin light chain kinase inhibitor ML-7 and the myosin ATPase inhibitor 2,3-butanedione-2-monoxime perturbed NF translocation within NB2a/d1 axonal neurites. These findings suggest that some NF subunits may undergo axonal transport via myosinmediated interactions with the actin cortex.

Inhalation of growth factors and apo-transferrin to protect and repair the hypoxic-ischemic brain

“…In support of this conclusion, a very low concentration of aTf was detected in the olfactory bulb when cytochalasine B or colchicine was administered before the INA of aTf. Colchicine inhibits microtubule assembly and reduces axonal transport [30], while, in the optic nerve, cytochalasin B is an inhibitor of neurofilament axonal transport [31]. However, further studies are necessary to describe the mechanism of transport of aTf from the olfactory area to the brain.…”

Computational Analysis of the Effects of Antineoplastic Agents on Axonal Transport

“…In contrast, cytochalasin B at 10 μM produced no effect. Cytochalasin B at 5 μM inhibits axonal transport of neurofilaments, which is dependent on actin and myosin (18). We examined the time course of changes in axonal transport before and after the application of these drugs.…”

“…Various kinds of therapeutic agents have neurological side effects, and some have been associated with the impairment of axonal transport (18). However, due to the lack of a valid method for the quantitative evaluation of axonal transport, systemic drug screening based on the effects on axonal transport has not been reported.…”

Differential roles of kinesin and dynein in translocation of neurofilaments into axonal neurites

“…Transport of NFs into and along axons requires an intact MT system Jung et al, 1998;Jung et al, 2004;Yabe et al, 2000) and the action of the MT motor proteins kinesin and dynein (He et al, 2005;Motil et al, 2006;Prahlad et al, 2000;Shah et al, 2000;Theiss et al, 2005;Uchida et al, 2009;Xia et al, 2003;Yabe et al, 1999;Yabe et al, 2000). As with other axonal constituents, kinesin mediates anterograde NF transport (Prahlad et al, 2000;Theiss et al, 2005;Xia et al, 2003;Yabe et al, 1999;Yabe et al, 2000), whereas dynein mediates retrograde transport (He et al, 2005;Motil et al, 2006;Shah et al, 2000;Theiss et al, 2005).…”

“…As with other axonal constituents, kinesin mediates anterograde NF transport (Prahlad et al, 2000;Theiss et al, 2005;Xia et al, 2003;Yabe et al, 1999;Yabe et al, 2000), whereas dynein mediates retrograde transport (He et al, 2005;Motil et al, 2006;Shah et al, 2000;Theiss et al, 2005). However, the dynamics of assembly and transport of NFs are complex; these MT-based motor proteins have multiple interactions with actin and the actin-based motor myosin Jung et al, 2004;Rao et al, 2002). Unexpectedly, the retrograde-directed motor dynein also participates in the anterograde delivery of NF forms into axonal neurites (Motil et al, 2006).…”