Human microtubule-associated-protein tau regulates the number of protofilaments in microtubules: A synchrotron X-ray scattering study

M. C. Choi, U. Raviv, H. P. Miller, M. R. Gaylord, E. Kiris, D. Ventimiglia, D. J. Needleman, M. W. Kim, L. Wilson, S. C. Feinstein, C. R. Safinya

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Abstract

Microtubules (MTs), a major component of the eukaryotic cytoskeleton, are 25 nm protein nanotubes with walls comprised of assembled protofilaments built from αβ 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 〈R MT〉 of MTs with increasing Φ, the tau/tubulin-dimer molar ratio. Within experimental scatter, the change in 〈RMT〉 seems to be isoform independent. Significantly, 〈RMT〉 was observed to rapidly increase for 0 < Φ < 0.2 and saturate for Φ 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 (=1/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.

Original languageAmerican English
Pages (from-to)519-527
Number of pages9
JournalBiophysical Journal
Volume97
Issue number2
DOIs
StatePublished - 2009

Bibliographical note

Funding Information:
This work was supported by the United States Department of Energy, Division of Material Sciences and Engineering (grant DOE DE-FG02-06ER46314 to C.R.S., M.C.C., U.R., D.J.N.), the United States National Science Foundation (grant NSF DMR-0803103 to C.R.S., M.C.C., U.R., D.J.N.), the National Institutes of Health (grants NS35010 to S.C.F., M.R.G., E.K., D.V., and NS13560 to L.W., H.P.M.), Korea Health 21 R&D Project MOHW (M.W.K.), the Korean Foundation (grant KRF-2005-2214-C00202 to M.C.C.), the International Human Frontier Science Program Organization (U.R.), and the International Human Frontier Science Program Organization Career Development Award (U.R.).

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