Date

2009-07-22

Author

Choi, MC
Raviv, U
Miller, HP
Gaylord, MR
Kiriş, Erkan
Ventimiglia, D
Needleman, DJ
Kim, MW
Wilson, L
Feinstein, SC
Safinya, CR

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This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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Microtubules (MTs), a major component of the eukaryotic cytoskeleton, are 25 nm protein nanotubes with walls comprised of assembled protofilaments built from ab heterodimeric tubulin. In neural cells, different isoforms of the microtubule-associated-protein (MAP) tau regulate tubulin assembly and MT stability. Using synchrotron small angle x-ray scattering (SAXS), we have examined the effects of all six naturally occurring central nervous system tau isoforms on the assembly structure of taxol-stabilized MTs. Most notably, we found that tau regulates the distribution of protofilament numbers in MTs as reflected in the observed increase in the average radius hRMTi of MTs with increasing F, the tau/tubulin-dimer molar ratio. Within experimental scatter, the change in hRMTi seems to be isoform independent. Significantly, hRMTi was observed to rapidly increase for 0 < F < 0.2 and saturate for F between 0.2–0.5. Thus, a local shape distortion of the tubulin dimer on tau binding, at coverages much less than a monolayer, is spread collectively over many dimers on the scale of protofilaments. This implies that tau regulates the shape of protofilaments and thus the spontaneous curvature Co MT of MTs leading to changes in the curvature CMT (¼1/RMT). An important biological implication of these findings is a possible allosteric role for tau where the tau-induced shape changes of the MT surface may effect the MT binding activity of other MAPs present in neurons. Furthermore, the results, which provide insight into the regulation of the elastic properties of MTs by tau, may also impact biomaterials applications requiring radial size-controlled nanotubes.

Subject Keywords

Resolution, Inhibition, 4-Repeat-tau, 3-Repeat-tau, Tubulin, Neurite outgrowth, Binding domains, Dynamic instability, Kinetic stablization, Paired helical filaments

URI

https://hdl.handle.net/11511/32869

Collections

Department of Biology, Article