Cell and Developmental Biology University of Michigan

Research

Molecular and cellular mechanisms by which microtubules and associated motor proteins participate in vesicle transport and ciliary function.

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.

Lab Members

• John Dishinger
  Research Fellow
• Virupakshi Soppina
  Research Fellow
• Teresa Lynne Blasius
  Research Lab Technician
• Hooi Lynn Kee
  Graduate Student
• Stephen Norris
  Graduate Student

Publications

Representative Publications

Representative Publications

• Friedman JR, Webster BM, Mastronarde DN, Verhey KJ, and Voeltz GK.  2010.   ER sliding dynamics and ER-mitochondrial contacts occur on acetylated microtubules.   Journal of Cell Biology 190: 363-375.  PMID 20696706.
• Dishinger JF, Kee HL, Jenkins PM, Fan SL, Hurd TW, Hammond JW, Truong YNT, Margolis B, Martens JR, and Verhey KJ.  2010.   Ciliary entry of the kinesin-2 motor KIF17 is regulated by importin-b2 and Ran-GTP .  Nature Cell Biology 12: 703-710.  PMID 20526328.
• Verhey KJ and Hammond JH.  2009.   Trraffic control: Regulation of kinesin motors .  Nature Reviews Molecular Cell Biology. 10: 765-777. PMID: 19851335.
• Hammond JW, Blasius TL, Soppina V, Cai D, and Verhey KJ.  2010.   Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms.   Journal of Cell Biology 189: 1013-1025.  PMID 20530208.
• Hammond JW*, Huang C-F *, Kaech S, Jacobson C, Banker G, and Verhey KJ.  2010.   Posttranslational modifications of tubulin and the polarized transport of Kinesin-1 in neurons .  Molecular Biology of the Cell. 21: 572-583.  PMID 20032309.
• Cai D, McEwen DP, Martens JR, Meyhofer E, and Verhey KJ.  2009.   Single molecule imaging reveals differences in microtubule track selection between Kinesin motors .  PLoS Biology 7: e1000216.  PMID: 19823565.
• Qian M*, Cai D*, Verhey KJ, and Tsai B.  2009.   A lipid receptor sorts polyomavirus from the endolysosome to the endoplasmic reticulum to cause infection .  PLoS Pathogen 5: e1000465. PMID: 19503604.
• Hammond JW, Cai D, Blasius TL, Li Z, Jiang Y, Jih GT, 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.   Co-operative versus independent transport of different cargoes by Kinesin-1 .  Traffic 9: 725-741.  PMID: 18266909.
• Cai D, Verhey KJ, and Meyhöfer E.  2007.   Tracking single Kinesin molecules in the cytoplasm of mammalian cells .  Biophysical Journal. 92: 4137-4144.  PMID: 17400704.
• Cai D, Hoppe AD, Swanson JA, and Verhey KJ.  2007.   Kinesin-1 structural organization and conformational changes revealed by FRET stoichiometry in live cells .  Journal of Cell Biology. 176: 51-63.  PMID: 17200416.  
• Blasius TL, Cai D, Jih GT, Toret CP, and Verhey KJ.  2007.   Two binding partners cooperate to activate the molecular motor kinesin-1. Journal of Cell Biology . 176: 11-17.  PMID: 17200414.
• Reed NA, Cai D, Blasius TL, Jih GT, Meyhofer E, Gaertig J, and Verhey KJ.  2006.   Microtubule acetylation promotes kinesin-1 binding and transport .  Current Biology. 16: 2166-2172.  PMID: 17084703
• Jenkins PM, Hurd TW, Zhang L, McEwen DP, Brown RL, Margolis B, Verhey KJ, and Martens JR.  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.
• Soppina V, Herbstman JF, Skiniotis G, Verhey KJ. 2012. Luminal localization of a-tubulin acetylation by cryo-EM analysis of Fab-labeled microtubules. PLoS One. 7(10):e48204.
• Kee HL, Dishinger JF, Blasius TL, Liu CJ, Margolis B, Verhey KJ. 2012. A size-exclusion permeability barrier and nucleoporins characterize a ciliary pore complex that regulates transport into cilia. Nat Cell Biol. 14(4):431-7.
• Hammond JW, Blasius TL, Soppina V, Cai D, Verhey KJ. 2010. Autoinhibition of the kinesin-2 motor KIF17 via dual intramolecular mechanisms. J Cell Biol. 189(6):1013-25
• Dishinger JF, Kee HL, Jenkins PM, Fan S, Hurd TW, Hammond JW, Truong YN, Margolis B, Martens JR, Verhey KJ. 2010. Ciliary entry of the kinesin-2 motor KIF17 is regulated by importin-b2 and RanGTP. Nat Cell Biol. 12(7):703-10.
• Hammond JW, Huang CF, Kaech S, Jacobson C, Banker G, Verhey KJ. 2010. Posttranslational modifications of tubulin and the polarized transport of kinesin-1 in neurons. Mol Biol Cell. 21(4):572-83.
• Cai D, McEwen DP, Martens JR, Meyhofer E, Verhey KJ. 2009. Single molecule imaging reveals differences in microtubule track selection between kinesin motors. PLoS Biol. 7(10):e1000216.
• Hammond JW, Cai D, Blasius TL, Li Z, Jiang Y, Jih GT, Meyhofer E, Verhey KJ. 2009. Mammalian kinesin-3 motors are dimeric in vivo and move by processive motility upon release of autoinhibition. PLoS Biol. 31;7(3):e72.
• Hammond JW, Griffin K, Jih GT, Stuckey J, Verhey KJ. 2008. Co-operative versus independent transport of different cargoes by kinesin-1. Traffic. 9(5):725-41.
• Cai D, Verhey KJ, Meyhöfer E. 2007. Tracking single kinesin molecules in the cytoplasm of mammalian cells. Biophys J. 92(12):4137-44.
• Cai D, Hoppe AD, Swanson JA, Verhey KJ. 2007. Kinesin-1 structural organization and conformational changes revealed by FRET stoichiometry in live cells. J Cell Biol. 176(1):51-63.
• Blasius TL, Cai D, Jih GT, Toret CP, Verhey KJ. 2007. Two binding partners cooperate to activate the molecular motor Kinesin-1. J Cell Biol. 176(1):11-7.

Reviews
• Verhey KJ, Kaul N, and Soppina V. 2011. Kinesin Assembly and Movement in Cells. Ann Rev Biophysics 40: 267-288. PMID 21332353.
• Cai D, Kaul N, Lionberger TA, Wiener DM, Verhey KJ, and Meyhofer E. 2010. Recording single motor proteins in the cytoplasm of mammalian cells . Methods in Enzymology 475:81-107. PMID 20627154.
• Hammond JW, Cai D, and Verhey KJ. 2008. Tubulin modifications and their cellular functions . Current Opinion in Cell Biology. 20: 71-76. PMID: 18226514.
• Verhey KJ. 2007. Motor proteins: trafficking and signaling collide . Current Biology. 17: R804-806. PMID: 17878049.
• Verhey KJ and Gaertig J. 2007. The tubulin code . Cell Cycle. 6:2152-2160. PMID: 17786050.
• Verhey KJ and Rapoport TA. 2001. Kinesin carries the signal . TRENDS in Biochemical Sciences 26: 545-550.