Tubulin-Specific Chaperones

Mutant Tbce mice. Progressive motor neuropathy (PMN), an autosomal recessive murine disease, manifests as weakness beginning within a few weeks of birth [14, 136]. These mice are homozygous for a Trp 524 Gly substitution of Tbce (tubulin-specific chaperone E), localized to mouse chromosome 13 [14]. Tbce mRNA is present in neurons in the spinal cord. Degenerative changes are conspicuous in motor axons, and ultrastructural studies of peripheral nerves of PMN mice disclose reduced numbers of microtubules in these axons. Mutations of the highly conserved Trp524 residue, which appears to influence... 

Tubulin-specific chaperone Sp Kenny-Caffey syndrome/ HRD... 

Bommel, H., Xie, G., Rossoll, W., Wiese, S., Jablonka, S., Boehm, T., et al. (2002) Missense mutation in the tubulin-specific chaperone E (Tbce) gene in the mouse mutant progressive motor neuronopathy, a model of human motoneuron disease. J Cell Biol 159, 563-569. 

TYPE II CHAPERONINS, PREFOLDIN, AND THE TUBULIN-SPECIFIC CHAPERONES... 

The principal targets for facilitated folding by CCT in cooperation with prefoldin are the cytoskeletal proteins actin and tubulin. The actin monomer assembles into microfilaments, while the subunit that forms microtubules is the tubulin heterodimer, which consists of a single a- and a single /f-tubulin polypeptide. Though actin can be folded to the native state via one or more cycles of ATP-dependent interaction with CCT, this is not the case for either a- or /Ttubulin. Tubulin subunits released from CCT are assembled into a/fi heterodimers by interaction with several tubulin-specific chaperones known as cofactors in a reaction that depends on GTP hydrolysis by the cofactor-bound tubulin. 

Fig. 3. Only CCT (but not GroEL) can productively fold actin or tubulin. Binary complexes formed in vitro between GroEL and unfolded /bactin (A, B) or a-tubulin (C) were incubated in the presence of GroES, ATP (A, B) or ATP, GTP and tubulin-specific chaperones (C), and an eightfold molar excess of CCT (B, C). After the incubation times (in minutes) shown, the reaction products were analyzed by nondenaturing gel electrophoresis. Arrows (top to bottom) show the location of CCT binary complexes, GroEL binary complexes, and either native actin or native tubulin heterodimers. Adapted from Tian et al. (1995b), with permission.

Bartolini, F., Bhamidipati, A., Thomas, S., Schwahn, U., Lewis, S. A., and Cowan, N. J. (2002). Functional overlap between retinitis pigmentosa 2 protein and the tubulin-specific chaperone cofactor C. J. Biol. Chem. 277, 14629-14634. 

Protein folding is the result of interactions among very weak chemical attractions. Proteins have evolved to fold in conditions present in the cells. In some cases, chaperone proteins are required to help other proteins to fold properly. The structural proteins actin and tubulin cannot fold without their specific chaperonins present (King et al., 2002). 

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