Michelle Moritz

Department of Biochemistry & Biophysics
University of California, San Francisco
600 16th St, Room S416
San Francisco CA
(415) 502-2930 (Ph)
(415) 476-1902 (Fax)

The Structure and Biochemistry of the γ-Tubulin Ring Complex

I am studying the mechanism of microtubule nucleation from the highly conserved γ-tubulin ring complex (γTuRC) of the centrosome and other microtubule-organizing centers (MTOCs). I am focusing on the structure-function relationship of the arrangement of γ-tubulins within the γTuRC to microtubule-nucleating activity. I have found that a “closed” γTuRC conformation is more active than an “open” conformation, which suggests a point of regulation for microtubule nucleating activity (Kollman et al 2015, Nat Struc Mol Biol 22:132). A promising candidate for a regulator is casein kinase 1δ (Hrr25p in S. cerevisiae), a member of the highly conserved casein kinase family. It associates with MTOCs in many organisms, but its specific targets and roles in MTOCs have yet to be defined. We found that Hrr25p localizes to the yeast centrosome/spindle pole body and phosphorylates the (γTuSC) in vivo and in vitro. Hrr25p kinase activity is important for normal microtubule function and spindle positioning in vivo. In vitro microtubule assembly experiments revealed that Hrr25p enhances the microtubule nucleating activity of the yeast γTuRC (Peng et al (2015) MBoC 26:2505). To better understand the interaction of Hrr25p and γTuSC on a molecular level, we are pursuing a structural study by single-particle cryo-electron microscopy.

I am also involved in the experimental side of our kinetic modeling of microtubule nucleation by collecting microtubule assembly data through turbidity, TIRF, and DIC microscopy under various conditions. Our aim is to test the effects of mutations in γ- and αβ-tubulin on the mechanism of nucleation and assembly, as well as to assess the contributions of regulatory molecules such as Hrr25p.


Lyon, A.S., G. Morin, M. Moritz, K.C.B. Yabut, T. Vojnar, A. Zelter, E. Muller, T.N. Davis, D.A. Agard. 2016. Higher-order oligomerization of Spc110p drives γ-tubulin ring complex assembly. Mol. Biol. Cell. 27: 2245-2258.pdf

Peng, Y., M. Moritz, X. Han, T.H. Giddings, A. Lyon, J. Kollman, M. Winey, J. Yates III, D.A. Agard, D.G. Drubin, G. Barnes. 2015. Interaction of CK1δ with γTuSCensures proper microtubule assembly and spindle positioning. Mol. Biol. Cell. 26:2505-2518.pdf

Kollman, J. M., C. H. Greenberg, S. Li, M. Moritz, A. Zelter, K. K. Fong, J. J. Fernandez, A. Sali, J. Kilmartin, T. N. Davis and D. A. Agard. 2015. Ring closureactivates yeast γTuRC for species-specific microtubule nucleation. Nat Struct Mol Biol 22(2): 132-137.pdf

GCP5 and GCP6: Two New Members of the Human γ-Tubulin Complex, Murphy, S.M, Preble, A.M., Patel, U.K., O'Connell, K.L., Dias, D.P., Moritz, M., Agard, D.A., Stults, J.T., and Stearns, T. Mol. Biol. Cell 2001;12 3340-3352, html or pdf.

M. Moritz, M.B. Braunfeld, B.M. Alberts, D.A. Agard, "Reconstitution of Centrosome Microtubule Nucleation in Drosophila," Methods in Cell Biology. (2001) 67:141-8.

M. Moritz and D.A. Agard, "γ-Tubulin Complexes and Microtubule Nucleation," Current Opinion in Structural Biology, 2001 Apr;11(2):174-81 (pdf or html).

M. Moritz, Braunfeld MB, Guenebaut V, Heuser J, Agard DA. "Structure of the g-tubulin ring complex: a template for microtubule nucleation," Nat Cell Biol. 2000 2(6), 365-70 (Abstract)

M. Moritz "Preparing cytoplasmic extracts from Drosophila embryos. In Drosophila: A laboratory manual," 2000, Ashburner, M. (ed.), Cold Spring Harbor Laboratory Press. 571-5.

M. Moritz and B.M. Alberts, "Isolation of centrosomes from Drosophila embryos," Methods in Cell Biol.,1998, 61, 1-12.

M. Moritz, Y. Zheng, B.M. Alberts, and K. Oegema, "Recruitment of the gamma-tubulin ring complex to Drosophila salt-stripped centrosome scaffolds," J. Cell Biol.,1998, 142, 775-786.

M. Moritz, M.B. Braunfeld, J.W. Sedat, B.M. Alberts, and D.A. Agard, "Microtubule nucleation by γ-tubulin-containing rings in the centrosome," Nature, 1995, 378, 638-40.

M. Moritz, M.B. Braunfeld, J.C. Fung, J.W. Sedat, B.M. Alberts, and D.A. Agard, "Three-dimensional structural characterization of centrosomes from early Drosophila embryos," J. Cell Biol.,1995, 130, 1149-59 Abstract.

D.R. Kellogg, M. Moritz, and B.M. Alberts, "The centrosome and cellular organization," Annu. Rev. Biochem.,1994, 63, 639-74.

M. Moritz, "Watching the tube," Current Biology, 1993, 3, 387-390.

M. Moritz, B.A. Pulaski, and J.L. Woolford, Jr., "Assembly of 60S ribosomal subunits is perturbed in temperature-sensitive mutants defective in yeast ribosomal protein L16," Mol. Cell. Biol., 1991, 11, 5681-5692.

M. Moritz,, A.G. Paulovich, Y.-F. Tsay, and J.L. Woolford, Jr., "Depletion of yeast ribosomal proteins L16 or rp59 disrupts ribosome assembly," J. Cell Biol., 1990, 111, 2261-2274 Abstract.

M.O. Rotenberg, M. Moritz, and J.L. Woolford, Jr., "Depletion of Saccaharomyces cerevisiae ribosomal protein L16 causes a decrease in 60S ribosomal subunits and formation of half-mer polyribosomes," Genes & Development, 1988, 2, 160-172.
Review Articles
Moritz, M. and D.A. Agard. 2001. γ-Tubulin complexes and microtubule nucleation. Current Opinion in Structural Biology 11(2):174-181. 

Kellogg, D.R., M. Moritz, and B.M. Alberts. 1994. The centrosome and cellular organization. Annu. Rev. Biochem. 63:639-74. 

Moritz, M. 1993. Watching the tube. Current Biology 3:387-390.

Book Chapters
Moritz, M. 2007. Preparing cytoplasmic extracts from Drosophila embryos. In CSH Drosophila Protocols, Mar. 1, Sullivan, W., Ashburner, M, Hawley, R.S.,editors, CSH Press pp. 571-575. 

Moritz, M., L.M. Rice, and D.A. Agard. 2004. Microtubule nucleation. In Centrosomes in Development and Disease. Nigg, E.A., editor, Wiley-VCH. pp. 27-41. 

Moritz, M., M.B. Braunfeld, B.M. Alberts, D.A. Agard. 2001. Reconstitution of centrosome nucleation in Drosophila. In Methods in Cell Biology 67:141-148. 

Moritz M. Drosophila Protocols. Sullivan W, Ashburner M, Hawley RS, editors. Cold Spring Harbor, New York: Cold Spring Harbor Laboratory Press; 2000. Chapter 33, Preparing Cytoplasmic Extracts from Drosophila Embryos; p.571-575. 

Moritz, M. and B.M. Alberts. 1998. Isolation of centrosomes from Drosophila embryos. Methods in Cell Biol. 61: 1-12.