Cell and Developmental Biology University of Michigan

Microtubules are cytoskeletal filaments that provide structural support for cells and also play important roles in cells as they serve as tracks for vesicle transport, form the mitotic spindle for separation of chromosomes during cell division, and comprise the axoneme in cilia and flagella. Defects in these microtubule-based functions are associated with a variety of diseases, including neurodegeneration, cancer, and ciliopathies. Our work is focused on the molecular and cellular mechanisms by which microtubules and associated motor proteins participate in vesicle transport and ciliary function. Motor proteins use the energy of ATP hydrolysis to carry cargoes along microtubule tracks. This is an essential function in all cells but is particular important in polarized cells such as neurons which have a high transport load due to the long distances and choice of direction (axon versus dendrite) that cargoes must be carried. Our work in axonal transport is focused on how kinesin motor proteins bind to their cargoes and become activated for transport. We are also interested in how directional choices are made by kinesin motors and are exploring the hypothesis that there is a “tubulin code” in which post-translational modifications of subsets of microtubules provide directional cues to kinesin motors. Our work in cilia is focused on the role of kinesin motors in the assembly, function and disassembly of primary cilia during the G1 phase of the cell cycle.

Publications

Representative Publications

Research
• Cai D, McEwen D, Martens JR, Meyhofer E, and Verhey KJ. 2009.  Single Molecule Imaging Reveals Differences in Microtubule Track Selection by Kinesin Motors.  PLoS Biology 7: e1000216.  doi:10.1371/journal.pbio.1000216
• Hammond JW, Cai D, Blasius TL, Li Z, Jiang Y, Jih G, Meyhofer E, and Verhey KJ.  2009.  Mammalian Kinesin-3 motors are dimeric in vivo and move by processive motility upon release of autoinhibition.  PLoS Biology 7: e72.  PMID: 19338388.
• Hammond JW, Griffin K, Jih GT, Stuckey J, and Verhey KJ.  2008.  Cooperative versus Independent transport of Kinesin-1 cargoes.  Traffic 9: 725-741.  PMID: 18266909.
• Cai DW, KJ Verhey, and E Meyhofer.  2007.  Tracking Single Kinesin Molecules in the Cytoplasm of Mammalian Cells.  Biophysical Journal 92: 4137-4144.  PMID: 17400704
• Blasius TL, D Cai, GT Jih, CP Toret, and KJ Verhey.  2007.  Two binding partners cooperate to activate the molecular motor Kinesin-1.  Journal of Cell Biology 176: 11-17.  PMID: 17200414.
• Cai D, AD Hoppe, JA Swanson, and KJ Verhey.  2007.  Kinesin-1 Structural Organization and Conformational Changes Revealed by FRET Stoichiometry in Live Cells.  Journal of Cell Biology 176: 51-63.  PMID: 17200416
• Reed NA, D Cai, TL Blasius, GT Jih, E Meyhofer, J Gaertig, and KJ Verhey.  2006.  Microtubule acetylation promotes Kinesin-1 binding and transport.  Current Biology 16: 2166-2172.  PMID: 17084703.
• Jenkins PM, TW Hurd, L Zhang, DP McEwen, RL Brown, B Margolis, KJ Verhey, and JR Martens.  2006.  Ciliary targeting of olfactory CNG channels requires the CNGB1b subunit and the kinesin-2 motor protein, KIF17.  Current Biology 16: 1211-1216.  PMID: 16782012.

Reviews
• Verhey KJ and Hammond JW.  2009.  Traffic control: Regulation of Kinesin Motors.  Nat Rev Mol Cell Biol, in press.
• Hammond JW, Cai D, and Verhey KJ.  2008.  Tubulin modifications and their cellular functions.  Current Opinion in Cell Biology 20: 71-76.  PMCID:2274889.
• Verhey KJ and Gaertig J.  2007.  The tubulin code.  Cell Cycle 6: 2152-2160.  PMID: 17786050