Study the Cellular Functions of Tubulin Chaperone E

Project Details

Description

Summary The tubulin cofactor E (TBCE) gene encodes a chaperone required for the folding of -tubulin subunits and the formation of native / tubulin heterodimers. Mutations in TBCE cause a severe syndrome of Hypoparathyroidism, Retardation and Dysmorphism (HRD). The pathophysiological connection between impairment of the tubulin chaperone function of TBCE and the phenotype of HRD patients is not obvious. Based on our joint investigation, we have been able to establish that TBCE interacts with a range of non-tubulin proteins and that it can shuttle between intracellular compartments, permitting it to engage in cell cycle-regulated interactions. We have been able to show that TBCE interacts with microtubule dynamics regulators via carboxy- and amino-terminal structural motifs, whereas a central leucine-rich repeat domain appears to mediate nuclear entry by TBCE. The common deletion mutation in the amino-terminal cytoskeleton-associated protein/glycine-rich (CAP-gly) domain has a minimal effect on tubulin folding but a major effect on interaction with the microtubule dynamics regulator p150glued. A potential role for the nuclear localization is suggested by the possible interaction of TBCE with a mitotic regulatory protein. Our findings provide evidence that the HRD phenotype is not caused by a quantitative lack of properly folded tubulin, but rather that the mutation of TBCE impairs a number of novel functions. These findings suggest that TBCE can integrate tubulin folding with microtubule assembly through interactions with known regulators of microtubule dynamics and suggest an entirely unexpected and uncharacterized role for this protein in the nucleus.

StatusActive
Effective start/end date1/01/05 → …

Funding

  • United States-Israel Binational Science Foundation: $107,000.00

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.