Department of Molecular and Cellular Biology, College of Biological Sciences
I have a long-standing research interest in the cytoskeleton, and in particular the motor proteins that utilize the cytoskeleton as tracks for intracellular transport. I was fortunate to have an opportunity at basic research beginning early in my undergraduate career, where I worked on signaling pathways related to cancer. This work afforded me valuable, early experience in the lab, and confirmed to me that I wanted to pursue research as a career. I pursued graduate research focused on the mechanochemical regulation of the microtubule motor cytoplasmic dynein. At Columbia University, I joined the lab of Dr. Richard Vallee, who discovered the motor protein cytoplasmic dynein. My work was the first to describe how two regulatory proteins, LIS1 and NudE, are able to modulate dynein’s motor output, transforming it from a weak to a persistent motor. This work combined biochemistry and biophysical approaches to provide insights into long-standing questions in the dynein and brain development fields, as LIS1 is the causative gene of the neurodevelopmental disease lissencephaly. I then moved to the lab of Dr. Ron Vale at UCSF to continue my studies on dynein using advanced single molecule microscopy. In Ron's lab I have made several contributions to the dynein field, including how dynein organizes microtubule networks, how it is activated and linked to cargo through the dynactin complex and adapter proteins, and how its motor activity is directly influenced by post-translational modification of the microtubule track itself.
Motor proteins and the cytoskeleton
My lab is interested in the fascinating world of molecular movement. We study how cells internally organize using molecular motor proteins. In particular, we focus on the microtubule cytoskeleton and the motor proteins that use this filament system for transport (kinesins and dyneins). We are interested in allosteric regulation of motor protein movement, how motor activity is balanced and coordinated, and how dysfunction in motor activity leads to human diseases such as cancer and neurodegeneration. The lab combines advanced molecular biology, biochemistry and single-molecule TIRF microscopy to address these problems.
Grad Group Affiliations
- Biochemistry, Molecular, Cellular and Developmental Biology
Specialties / Focus
- Cell Biology
- Cell Division and the Cytoskeleton
Honors and Awards
- NIH Pathway to Independence Award (K99/R00 - NINDS)
- NIGMS Maximizing Investigators' Research Award (MIRA) (R35)
- March of Dimes Basil O'Connor Starter Scholar Award
- 2010 Ph.D. Pathology and Cell Biology Columbia University
- 2002 B.S. Biology Xavier University
Microtubules gate tau condensation to spatially regulate microtubule functions.
Tan R, Lam AJ, Tan T, Han J, Nowakowski DW, Vershinin M, Simó S, Ori-McKenney KM, McKenney RJ.
Nat Cell Biol. 2019 Sep;21(9):1078-1085. doi: 10.1038/s41556-019-0375-5. Epub 2019 Sep 2.
Disease-associated mutations hyperactivate KIF1A motility and anterograde axonal transport of synaptic vesicle precursors.
Chiba K, Takahashi H, Chen M, Obinata H, Arai S, Hashimoto K, Oda T, McKenney RJ, Niwa S.
Proc Natl Acad Sci U S A. 2019 Aug 27. pii: 201905690. doi: 10.1073/pnas.1905690116. [Epub ahead of print]
Tau repeat regions contain conserved histidine residues that modulate microtubule-binding in response to changes in pH.
Charafeddine RA, Cortopassi WA, Lak P, Tan R, McKenney RJ, Jacobson MP, Barber DL, Wittmann T.
J Biol Chem. 2019 May 31;294(22):8779-8790. doi: 10.1074/jbc.RA118.007004. Epub 2019 Apr 16.
Agarwal S, Smith KP, Zhou Y, Suzuki A, McKenney RJ, Varma D. Cdt1 stabilizes
kinetochore-microtubule attachments via an Aurora B kinase-dependent mechanism. J
Cell Biol. 2018 Aug 28. pii: jcb.201705127. doi: 10.1083/jcb.201705127. [Epub
ahead of print] PubMed PMID: 30154187.
Karasmanis EP, Phan CT, Angelis D, Kesisova IA, Hoogenraad CC, McKenney RJ,
Spiliotis ET. Polarity of Neuronal Membrane Traffic Requires Sorting of Kinesin
Motor Cargo during Entry into Dendrites by a Microtubule-Associated Septin. Dev
Cell. 2018 Jul 16;46(2):204-218.e7. doi: 10.1016/j.devcel.2018.06.013.
Tjioe M, Ryoo H, Ishitsuka Y, Ge P, Bookwalter C, Huynh W, McKenney RJ, Trybus
KM, Selvin PR. Magnetic Cytoskeleton Affinity (MiCA) Purification of Microtubule
Motors conjugated to Quantum Dots. Bioconjug Chem. 2018 Jun 22. doi:
10.1021/acs.bioconjchem.8b00264. PubMed PMID: 29932650.
Amin MA, McKenney RJ, Varma D. Antagonism between the dynein and Ndc80
complexes at kinetochores controls the stability of kinetochore-microtubule
attachments during mitosis. J Biol Chem. 2018 Feb 23. pii: jbc.RA117.001699. doi:
10.1074/jbc.RA117.001699. PubMed PMID: 29475948.
Grotjahn DA, Chowdhury S, Xu Y, McKenney RJ, Schroer TA, Lander GC.
Cryo-electron tomography reveals that dynactin recruits a team of dyneins for
processive motility. Nat Struct Mol Biol. 2018 Mar;25(3):203-207. doi:
10.1038/s41594-018-0027-7. Epub 2018 Feb 7. PMID: 29416113.
Tan R, Foster PJ, Needleman DJ, McKenney RJ. Cooperative Accumulation of Dynein-Dynactin at Microtubule Minus-Ends Drives Microtubule Network Reorganization. Dev Cell. 2018 Jan 22;44(2):233-247.e4. doi: 10.1016/j.devcel.2017.12.023. PMID: 29401420
Gutierrez PA, Ackermann BE, Vershinin M, McKenney RJ. Differential effects of the dynein-regulatory factor Lissencephaly-1 on processive dynein-dynactin motility. J Biol Chem. 2017 Jun 2. pii: jbc.M117.790048. doi: 10.1074/jbc.M117.790048.
Ori-McKenney KM, McKenney RJ, Huang HH, Li T, Meltzer S, Jan LY, Vale RD, Wiita AP, Jan YN. Phosphorylation of β-Tubulin by the Down Syndrome Kinase, Minibrain/DYRK1a, Regulates Microtubule Dynamics and Dendrite Morphogenesis. Neuron, 90, 1-13 (2016).
McKenney, RJ, Huynh, W, Vale, RD, Sirajuddin, M. (2016). Tyrosination of α-tubulin controls the initiation of processive dynein-dynactin motility. The EMBO J. Mar 11. Epub ahead of print.
- Faculty of 1000: Rated “Good” http://f1000.com/prime/726213598
- Perspective Article: Allan, V. J. (2016). A tale of two α-tubulin tails The EMBO Journal. DOI 10.15252/embj.201694325
McKenney, RJ, Huynh, W, Tanenbaum, ME, Bhabha, G, and Vale, RD (2014). Activation of cytoplasmic dynein motility by dynactin-cargo adapter complexes. Science. Jul 18;345(6194): 337-41. PMID: 25035494.
- Faculty of 1000: Rated “Very Good” http://f1000.com/prime/718496492
- Perspective Article: Allan, V. (2014). One, two, three, cytoplasmic dynein is go! Science. Jul 18;345(6194):271-2.
- Perspective Article: Cianfrocco, MA and Leschziner, AE (2014). Traffic control: adaptor proteins guide dynein–cargo takeoff. The EMBO Journal. Sep 1;33(17):1845-6.
- Perspective Article: Dodding, MP (2014). Backseat drivers: Cargo adaptors and dynactin activate cytoplasmic dynein motility. Cell Research. Aug. 22.
Tanenbaum ME*, Vale RD, McKenney RJ* (2013). Cytoplasmic Dynein Crosslinks and Slides Antiparallel Microtubules Using Its Two Motor Domains. eLife. (*equal contribution). Sep 3;2:e00943. PMCID: PMC3762337.
- Faculty of 1000: Rated “Very Good” http://f1000.com/prime/718101795
McKenney, RJ, Weil, SJ, Scherer, J, & Vallee, RB (2011). Mutually Exclusive Cytoplasmic Dynein Regulation by NudE-Lis1 and Dynactin. Journal of Biological Chemistry, 286(45), 39615–39622. PMID: 21911489.
Yi, JY, Ori-McKenney, KM, McKenney, RJ, Vershinin, M, Gross, SP, & Vallee, RB (2011). High-resolution imaging reveals indirect coordination of opposite motors and a role for LIS1 in high-load axonal transport. Journal of Cell Biology, 195(2), 193–201. PMID: 22006948.
Kunwar, A., Tripathy, SK, Xu, J, Mattson, MK, Anand, P, Sigua, R, Vershinin, M, McKenney, RJ, Yu CC, & Gross, SP (2011). Mechanical stochastic tug-of-war models cannot explain bidirectional lipid-droplet transport. PNAS, 108(47), 18960-18965. PMID: 22084076.
McKenney, RJ*, Vershinin, M*, Kunwar, A, Vallee, RB, & Gross, SP (2010). LIS1 and NudE induce a persistent dynein force-producing state. Cell, 141(2), 304–314. PMID: 20403325 (*equal contribution).
- Faculty of 1000: Rated “Very Good” http://f1000.com/prime/3110957
Stehman, SA, Chen, Y, McKenney, RJ, & Vallee, RB (2007). NudE and NudEL are required for mitotic progression and are involved in dynein recruitment to kinetochores. Journal of Cell Biology, 178(4), 583–594. PMID: 17682047.
Suzuki, SO, McKenney, RJ, Mawatari, S-Y, Mizuguchi, M, Mikami, A, Iwaki, T, Goldman, JE, Canoll, P, & Vallee RB. (2007). Expression patterns of LIS1, dynein and their interaction partners dynactin, NudE, NudEL and NudC in human gliomas suggest roles in invasion and proliferation. Acta Neuropathologica, 113(5), 591–599. PMID: 17221205.
Bahassi, EM, Myer, DL, McKenney, RJ, Hennigan, RF, & Stambrook, PJ (2006). Priming phosphorylation of Chk2 by polo-like kinase 3 (Plk3) mediates its full activation by ATM and a downstream checkpoint in response to DNA damage. Mutation research, 596(1-2), 166–176. PMID: 16481012.