Motor Domain Phosphorylation Modulates Kinesin-1 Transport

DeBerg, Hannah A.; Blehm, Benjamin H.; Sheung, Janet; Thompson, Andrew R.; Bookwalter, Carol S.; Torabi, Seyed Fakhreddin; Schroer, Trina A.; Berger, Christopher L.; Lu, Yi; Trybus, Kathleen M.; Selvin, Paul R.

doi:10.1074/jbc.m113.515510

Cited by 41 publications

(53 citation statements)

References 38 publications

(34 reference statements)

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“…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.…”

Section: Scaffolding Proteins Coordinate Motor Activitymentioning

confidence: 99%

Integrated regulation of motor-driven organelle transport by scaffolding proteins

Fu¹,

Holzbaur

2014

Trends in Cell Biology

251

264

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Intracellular trafficking pathways, including endocytosis, autophagy and secretion, rely on directed organelle transport driven by the opposing microtubule motor proteins kinesin and dynein. Precise spatial and temporal targeting of vesicles and organelles requires the integrated regulation of these opposing motors, which are often bound simultaneously to the same cargo. Recent progress demonstrates that organelle-associated scaffolding proteins, including Milton/TRAKs, JIP1, JIP3, huntingtin, and Hook1, interact with molecular motors to coordinate activity and sustain unidirectional transport. Scaffolding proteins also bind to upstream regulatory proteins including kinases and GTPases to modulate transport in the cell. This integration of regulatory control with motor activity allows for cargo-specific changes in the transport or targeting of organelles in response to cues from the complex cellular environment.

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Section: Scaffolding Proteins Coordinate Motor Activitymentioning

confidence: 99%

Integrated regulation of motor-driven organelle transport by scaffolding proteins

Fu¹,

Holzbaur

2014

Trends in Cell Biology

251

264

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“…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.…”

Section: Controlling the Transport Complex From The Bottom Upmentioning

confidence: 99%

“…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.…”

Section: Controlling the Transport Complex From The Bottom Upmentioning

confidence: 99%

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

Blehm

Selvin

2014

Chem. Rev.

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“…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.…”

Section: The Mechanism Of Halo Actionmentioning

confidence: 99%

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

Arora

Tran

Rizzo

et al. 2016

Journal of Cell Science

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During bidirectional transport, individual cargoes move continuously back and forth along microtubule tracks, yet the cargo population overall displays directed net transport. How such transport is controlled temporally is not well understood. We analyzed this issue for bidirectionally moving lipid droplets in Drosophila embryos, a system in which net transport direction is developmentally controlled. By quantifying how the droplet distribution changes as embryos develop, we characterize temporal transitions in net droplet transport and identify the crucial contribution of the previously identified, but poorly characterized, transacting regulator Halo. In particular, we find that Halo is transiently expressed; rising and falling Halo levels control the switches in global distribution. Rising Halo levels have to pass a threshold before net plus-end transport is initiated. This threshold level depends on the amount of the motor kinesin-1: the more kinesin-1 is present, the more Halo is needed before net plus-end transport commences. Because Halo and kinesin-1 are present in common protein complexes, we propose that Halo acts as a rate-limiting co-factor of kinesin-1.

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Motor Domain Phosphorylation Modulates Kinesin-1 Transport

Cited by 41 publications

References 38 publications

Integrated regulation of motor-driven organelle transport by scaffolding proteins

Integrated regulation of motor-driven organelle transport by scaffolding proteins

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

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

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