title: Human microtubule-associated-protein tau regulates the number of protofilaments in microtubules: a synchrotron x-ray scattering study.
abstract: Microtubules (MTs), a major component of the eukaryotic cytoskeleton, are 25 nm protein nanotubes with walls comprised of assembled protofilaments built from alphabeta 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 Phi, the tau/tubulin-dimer molar ratio. Within experimental scatter, the change in R(MT) seems to be isoform independent. Significantly, R(MT) was observed to rapidly increase for 0 < Phi < 0.2 and saturate for Phi 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 C(o)(MT) of MTs leading to changes in the curvature C(MT) (=1/R(MT)). 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.
authors.affiliation: Materials Department, University of California, Santa Barbara, California 93106, USA. mcchoi@mrl.ucsb.edu
authors.forename: M C
authors.initials: MC
authors.lastname: Choi
authors.forename: U
authors.initials: U
authors.lastname: Raviv
authors.forename: H P
authors.initials: HP
authors.lastname: Miller
authors.forename: M R
authors.initials: MR
authors.lastname: Gaylord
authors.forename: E
authors.initials: E
authors.lastname: Kiris
authors.forename: D
authors.initials: D
authors.lastname: Ventimiglia
authors.forename: D J
authors.initials: DJ
authors.lastname: Needleman
authors.forename: M W
authors.initials: MW
authors.lastname: Kim
authors.forename: L
authors.initials: L
authors.lastname: Wilson
authors.forename: S C
authors.initials: SC
authors.lastname: Feinstein
authors.forename: C R
authors.initials: CR
authors.lastname: Safinya
mesh_terms: D000818:Animals; D002417:Cattle; D002460:Cell Line; D004548:Elasticity; D006801:Humans; D008870:Microtubules / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular; D011189:Potassium Chloride / Q000494:pharmacology; D011485:Protein Binding / Q000187:drug effects; D020033:Protein Isoforms / Q000737:chemistry / Q000378:metabolism; D053838:Scattering, Small Angle; D055672:Static Electricity; D017356:Synchrotrons; D014961:X-Ray Diffraction; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020033:Protein Isoforms; D016875:tau Proteins; D011189:Potassium Chloride