Motor proteins carry cellular cargoes along the cytoskeleton to their destination. Disregulation of these processes underlies a number of diseases ranging from cancer to polycystic kidney disease to neurodegenerative diseases. The long-term goal of our research is to understand how motor protein transport is controlled and coordinated in cells. We will use molecular, biochemical and cell biological analyses to address the mechanisms that control cargo binding and motor activity of the microtubule-based motor kinesin-1. Our hypothesis is that spatially segregated protein complexes control kinesin-1 transport at the point of departure and at the destination. We will analyze the mechanisms by which cargo binding leads to motor activation at the point of departure. We will explore the possibility that modifications of the microtubule cytoskeleton play a role in directing motor protein transport to the correct cellular destination. We will analyze the role of newly-identified protein complexes in the release of cargo and inactivation of kinesin-1 at the destination. This work will provide exciting new insights into the function of kinesin-1 in nerve cells. This work will also increase our understanding of how the regulation of motor proteins gives rise to coordinated transport of protein complexes in cells and will suggest therapeutic targets in human disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM070862-03
Application #
7250249
Study Section
Cell Structure and Function (CSF)
Program Officer
Rodewald, Richard D
Project Start
2005-07-01
Project End
2010-06-30
Budget Start
2007-07-01
Budget End
2008-06-30
Support Year
3
Fiscal Year
2007
Total Cost
$236,777
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
073133571
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Yue, Yang; Blasius, T Lynne; Zhang, Stephanie et al. (2018) Altered chemomechanical coupling causes impaired motility of the kinesin-4 motors KIF27 and KIF7. J Cell Biol 217:1319-1334
Ravindran, Madhu Sudhan; Spriggs, Chelsey C; Verhey, Kristen J et al. (2018) Dynein engages and disassembles cytosol-localized SV40 to promote infection. J Virol :
Kelliher, Michael T; Yue, Yang; Ng, Ashley et al. (2018) Autoinhibition of kinesin-1 is essential to the dendrite-specific localization of Golgi outposts. J Cell Biol 217:2531-2547
Tymanskyj, Stephen R; Yang, Benjamin H; Verhey, Kristen J et al. (2018) MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport. Elife 7:
Muretta, Joseph M; Reddy, Babu J N; Scarabelli, Guido et al. (2018) A posttranslational modification of the mitotic kinesin Eg5 that enhances its mechanochemical coupling and alters its mitotic function. Proc Natl Acad Sci U S A 115:E1779-E1788
Yao, Xin-Qiu; Cato, M Claire; Labudde, Emily et al. (2017) Navigating the conformational landscape of G protein-coupled receptor kinases during allosteric activation. J Biol Chem 292:16032-16043
Breznau, Elaina B; Murt, Megan; Blasius, T Lynne et al. (2017) The MgcRacGAP SxIP motif tethers Centralspindlin to microtubule plus ends in Xenopus laevis. J Cell Sci 130:1809-1821
Atherton, Joseph; Jiang, Kai; Stangier, Marcel M et al. (2017) A structural model for microtubule minus-end recognition and protection by CAMSAP proteins. Nat Struct Mol Biol 24:931-943
Ravindran, Madhu Sudhan; Engelke, Martin F; Verhey, Kristen J et al. (2017) Exploiting the kinesin-1 molecular motor to generate a virus membrane penetration site. Nat Commun 8:15496
Skjærven, Lars; Jariwala, Shashank; Yao, Xin-Qiu et al. (2016) Online interactive analysis of protein structure ensembles with Bio3D-web. Bioinformatics 32:3510-3512

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