Abstract

Our efforts in the last year have concentrated on the microtubule severing enzyme spastin. Spastin is mutated in 40% of hereditary spastic paraplegias, a group of neurodegenerative disorders characterized by axonopathy. We have previously determined the X-ray structure of spastin and proposed a novel mechanism for microtubule severing (Roll-Mecak and Vale, 2008). We have made progress in the last year on Aim 1a of our research program that concentrates on understanding the biophysical mechanism of microtubule severing enzymes, specifically the interaction between spastin and the microtubule.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Investigator-Initiated Intramural Research Projects (ZIA)
Project #
1ZIANS003122-01
Application #
8158250
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2010
Total Cost
$1,240,813
Indirect Cost

  Institution

Name
National Institute of Neurological Disorders and Stroke
Department
Type
DUNS #
City
State
Country
Zip Code

  Publications

Sun, Xun; Park, James H; Gumerson, Jessica et al. (2016) Loss of RPGR glutamylation underlies the pathogenic mechanism of retinal dystrophy caused by TTLL5 mutations. Proc Natl Acad Sci U S A 113:E2925-34
Valenstein, Max L; Roll-Mecak, Antonina (2016) Graded Control of Microtubule Severing by Tubulin Glutamylation. Cell 164:911-21
Vemu, Annapurna; Atherton, Joseph; Spector, Jeffrey O et al. (2016) Structure and Dynamics of Single-isoform Recombinant Neuronal Human Tubulin. J Biol Chem 291:12907-15
Meyer, Peter A; Socias, Stephanie; Key, Jason et al. (2016) Data publication with the structural biology data grid supports live analysis. Nat Commun 7:10882
Garnham, Christopher P; Vemu, Annapurna; Wilson-Kubalek, Elizabeth M et al. (2015) Multivalent Microtubule Recognition by Tubulin Tyrosine Ligase-like Family Glutamylases. Cell 161:1112-1123
Yu, Ian; Garnham, Christopher P; Roll-Mecak, Antonina (2015) Writing and Reading the Tubulin Code. J Biol Chem 290:17163-72
Roll-Mecak, Antonina (2015) Intrinsically disordered tubulin tails: complex tuners of microtubule functions? Semin Cell Dev Biol 37:11-9
Vemu, Annapurna; Garnham, Christopher P; Lee, Duck-Yeon et al. (2014) Generation of differentially modified microtubules using in vitro enzymatic approaches. Methods Enzymol 540:149-66
Szyk, Agnieszka; Deaconescu, Alexandra M; Spector, Jeffrey et al. (2014) Molecular basis for age-dependent microtubule acetylation by tubulin acetyltransferase. Cell 157:1405-15
Szyk, Agnieszka; Piszczek, Grzegorz; Roll-Mecak, Antonina (2013) Tubulin tyrosine ligase and stathmin compete for tubulin binding in vitro. J Mol Biol 425:2412-4

Showing the most recent 10 out of 17 publications