Motor Domain Phosphorylation Modulates Kinesin-1 Transport

Abstract

Background: Kinesin-1 motor domain phosphorylation has been linked to impaired transport in axons. Results: A mechanism by which phosphorylation could affect transport is proposed. Conclusion: Phosphorylation decreases the stall force of kinesin and stabilizes autoinhibition. Significance: Kinesin phosphorylation could be used to fine tune the direction of cargo transport and contribute to pathology in neurodegenerative disease.

Integrated regulation of motor-driven organelle transport by scaffolding proteins

“…Mutant huntingtin induces the aberrant activation of neuronal-specific JNK3, a kinase that can phosphorylate KIF5C at S176 in vitro [57, 58]. Studies on phosphomutants (at the conserved KIF5B S175 site) indicate that while ATPase activity, microtubule-binding, and processivity are not altered, there is some enhanced autoinhibition of the phosphorylated kinesin motor that may favor minus-end-directed over plus-end-directed motility [59]. Thus, direct phosphorylation of molecular motors may also contribute to the tuning of transport, and this tuning may be altered in disease.…”

Single-Molecule Fluorescence and in Vivo Optical Traps: How Multiple Dyneins and Kinesins Interact

“…These assays have strongly demonstrated that pairs of motors (kinesin and mammalian dynein 12a , 12c , 13 or kinesin and yeast dynein) 11 undergo a tug-of-war in vitro without external signals or cofactors. In addition, when cofactors are examined in vitro with a motor (e.g.…”

“…12a , 13,23b In experiments by Muresan et al, using latex beads coated with kinesin and dynein, the beads always walked in the kinesin direction, i.e. bidirectional motility was not observed.…”

“…3C). 12a , 13 The fact that directional switching can be seen in both these systems without any external coordinating complex is strong support for a local tug-of-war, although it is difficult to say how similar other transport properties are between in vitro and in vivo systems.…”

Temporal control of bidirectional lipid-droplet motion in Drosophila depends on the ratio of kinesin-1 and its co-factor Halo

“…Because motor behaviour can be altered by phosphorylation (Hirokawa et al, 2009;DeBerg et al, 2013), Halo might control the phosphorylation state of kinesin-1 and, thus, its interaction with the switching mechanism. If Halo is counteracted by a ubiquitous kinase, then it would only be effective if present in high enough concentrations to outperform the kinase, possibly explaining both the threshold effect and the quick reversal of transport once Halo levels drop.…”