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Torsten Wittmann Ph.D.

Cytoskeletal dynamics, molecular and cell biology, live cell imaging

Torsten Wittmann Ph.D.

Dr. Wittmann's laboratory focuses on the function and spatiotemporal regulation of the microtubule cytoskeleton during complex cell behaviors. Microtubules are polymers that frequently switch between polymerization and depolymerization. These non-equilibrium dynamics may allow microtubule ends to explore the cytoplasm to interact with specific intracellular targets. We are interested in a fascinating group of proteins that are defined by their dynamic localization to growing microtubule ends in cells. The functions of these +TIPs are not well understood. In addition, it is quite mysterious how +TIPs recognize growing microtubule ends, and microtubule association of certain +TIPs is spatiotemporally regulated in cells. We use biochemical and cell biological techniques in combination with live cell confocal microscopy to examine how these and other cytoskeletal proteins determine cell behavior in different experimental model systems. This includes planar polarized keratinocytes that directionally migrate at the edge of epithelial cell sheets, apical-basal polarized epithelial cells in a three-dimensional extracellular matrix, and endothelial cells that establish planar polarity in response to fluid shear stress.

Selected publications:

1. Stehbens S, Wittmann T. Targeting and transport: How microtubules control focal adhesion dynamics. J Cell Biol. 2012 Aug 20; 198(4):481-9.

2. Kumar P, Wittmann T. +TIPs: SxIPping along microtubule ends. Trends Cell Biol. 2012 Aug; 22(8):418-28.

3. Gierke S, Wittmann T. EB1-Recruited Microtubule +TIP Complexes Coordinate Protrusion Dynamics during 3D Epithelial Remodeling. Curr Biol. 2012 May 8; 22(9):753-62.

4. Kumar P, Chimenti MS, Pemble H, Schönichen A, Thompson O, Jacobson MP, Wittmann T. Multisite Phosphorylation Disrupts Arginine-Glutamate Salt Bridge Networks Required for Binding of Cytoplasmic Linker-associated Protein 2 (CLASP2) to End-binding Protein 1 (EB1). J Biol Chem. 2012 May 18; 287(21):17050-64.

5. Stehbens S, Pemble H, Murrow L, Wittmann T. Imaging intracellular protein dynamics by spinning disk confocal microscopy. Methods Enzymol. 2012; 504:293-313.

6. Haynes J, Srivastava J, Madson N, Wittmann T, Barber DL. Dynamic actin remodeling during epithelial-mesenchymal transition depends on increased moesin expression. Mol Biol Cell. 2011 Dec; 22(24):4750-64.

7. Elwell CA, Jiang S, Kim JH, Lee A, Wittmann T, Hanada K, Melancon P, Engel JN. Chlamydia trachomatis co-opts GBF1 and CERT to acquire host sphingomyelin for distinct roles during intracellular development. PLoS Pathog. 2011 Sep; 7(9):e1002198.
View in: PubMed

8. Matov A, Applegate K, Kumar P, Thoma C, Krek W, Danuser G, Wittmann T. Analysis of microtubule dynamic instability using a plus-end growth marker. Nat Methods. 2010 Sep; 7(9):761-8.
View in: PubMed

9. Gierke S, Kumar P, Wittmann T. Analysis of microtubule polymerization dynamics in live cells. Methods Cell Biol. 2010; 97:15-33.
View in: PubMed

10. Kumar P, Lyle KS, Gierke S, Matov A, Danuser G, Wittmann T. GSK3beta phosphorylation modulates CLASP-microtubule association and lamella microtubule attachment. J Cell Biol. 2009 Mar 23; 184(6):895-908.

11. Lyle K, Kumar P, Wittmann T. SnapShot: Microtubule regulators II. Cell. 2009 Feb 6; 136(3):566, 566.e1.

12. Lyle K, Kumar P, Wittmann T. SnapShot: Microtubule Regulators I. Cell. 2009 Jan 23; 136(2):380, 380.e1. 

13. Wittmann T. EBs clip CLIPs to growing microtubule ends. J Cell Biol. 2008 Dec 29; 183(7):1183-5.

14. Delorme V, Machacek M, DerMardirossian C, Anderson KL, Wittmann T, Hanein D, Waterman-Storer C, Danuser G, Bokoch GM. Cofilin activity downstream of Pak1 regulates cell protrusion efficiency by organizing lamellipodium and lamella actin networks. Dev Cell. 2007 Nov; 13(5):646-62.

15. Kita K, Wittmann T, Näthke IS, Waterman-Storer CM. Adenomatous polyposis coli on microtubule plus ends in cell extensions can promote microtubule net growth with or without EB1. Mol Biol Cell. 2006 May; 17(5):2331-45.

16. Wittmann T, Waterman-Storer CM. Spatial regulation of CLASP affinity for microtubules by Rac1 and GSK3beta in migrating epithelial cells. J Cell Biol. 2005 Jun 20; 169(6):929-39.

17. Wittmann T, Desai A. Microtubule cytoskeleton: a new twist at the end. Curr Biol. 2005 Feb 22; 15(4):R126-9.

18. Shirasu-Hiza M, Perlman ZE, Wittmann T, Karsenti E, Mitchison TJ. Eg5 causes elongation of meiotic spindles when flux-associated microtubule depolymerization is blocked. Curr Biol. 2004 Nov 9; 14(21):1941-5.

19. Brunet S, Sardon T, Zimmerman T, Wittmann T, Pepperkok R, Karsenti E, Vernos I. Characterization of the TPX2 domains involved in microtubule nucleation and spindle assembly in Xenopus egg extracts. Mol Biol Cell. 2004 Dec; 15(12):5318-28.

20. Wittmann T, Bokoch GM, Waterman-Storer CM. Regulation of microtubule destabilizing activity of Op18/stathmin downstream of Rac1. J Biol Chem. 2004 Feb 13; 279(7):6196-203.

For more information regarding Dr. Wittmann, please visit: http://wittmann.ucsf.edu/index.html