Antonina Roll-Mecak, Ph.D.
Cell Biology and Biophysics Section
Building 35, Room 3B203
35 Convent Drive
Bethesda, MD 20892-3700
In addition to providing structural support, microtubules form a complex and dynamic intracellular "highway" that delivers molecular cargo from one end of the cell to another -which in the case of neuronal cells can span several feet. Given the continually changing cell physiology, this delivery system undergoes constant remodeling as cargo is transported to different destinations with high temporal and spatial accuracy. Failures in this highly coordinated transport system lead to disease and mutations in genes that encode microtubule dynamics regulators have been implicated in neurodegeneration, cardiovascular disease, cancers and viral infections.
Not surprisingly, tubulin, the building block of the microtubule network is one of the most post-translationally modified proteins in the cell. My laboratory combines biophysical and cell biological approaches to understand the interplay between microtubules and their regulators and how the chemical complexity of microtubules tunes the behavior of motors and microtubule associated proteins. Despite the abundance and complexity of tubulin modifications, their effects on microtubule behavior are still poorly understood. Is the microtubule more than just a structural strut, or a naive roadway for cellular components to transit along? Is there a "tubulin code", written in the rich language of the post-translational modifications of tubulin that, much like a histone code, provides specificity and regulation to cellular dynamics and to the trafficking of motor proteins and their cargo on the cellular highway? How functional diversity is imparted to different microtubules is a central question in cell biology with important implications for human health.
Valenstein ML, Roll-Mecak A. Graded Control of Microtubule Severing by Tubulin Glutamylation. Cell. 2016;164(5):911-21.
Garnham CP, Vemu A, Wilson-Kubalek EM, Yu I, Szyk A, Lander GC, Milligan RA, Roll-Mecak A. Multivalent Microtubule Recognition by Tubulin Tyrosine Ligase-like Family Glutamylases. Cell. 2015;161(5):1112-1123.
Vemu A, Atherton J, Spector JO, Szyk A, Moores CA, Roll-Mecak A. Structure and Dynamics of Single-isoform Recombinant Neuronal Human Tubulin. J Biol Chem. 2016;291(25):12907-15.
Zehr E, Szyk A, Piszczek G, Szczesna E, Zuo X, Roll-Mecak A. Katanin spiral and ring structures shed light on power stroke for microtubule severing. Nat Struct Mol Biol. 2017.
Garnham CP, Yu I, Li Y, Roll-Mecak A. Crystal structure of tubulin tyrosine ligase-like 3 reveals essential architectural elements unique to tubulin monoglycylases. Proc Natl Acad Sci U S A. 2017;114(25):6545-6550.
Related Scientific Focus Areas
Biomedical Engineering and Biophysics
This page was last updated on March 1st, 2018