title: Paclitaxel suppresses Tau-mediated microtubule bundling in a concentration-dependent manner.
abstract: Microtubules (MTs) are protein nanotubes comprised of straight protofilaments (PFs), head to tail assemblies of αβ-tubulin heterodimers. Previously, it was shown that Tau, a microtubule-associated protein (MAP) localized to neuronal axons, regulates the average number of PFs in microtubules with increasing inner radius <RinMT> observed for increasing Tau/tubulin-dimer molar ratio ΦTauat paclitaxel/tubulin-dimer molar ratio ΛPtxl=1/1.
  
  
  
  We report a synchrotron SAXS and TEM study of the phase behavior of microtubules as a function of varying concentrations of paclitaxel (1/32≤ΛPtxl≤1/4) and Tau (human isoform 3RS, 0≤Φ3RS≤1/2) at room temperature.
  
  
  
  Tau and paclitaxel have opposing regulatory effects on microtubule bundling architectures and microtubule diameter. Surprisingly and in contrast to previous results at ΛPtxl=1/1 where microtubule bundles are absent, in the lower paclitaxel concentration regime (ΛPtxl≤1/4), we observe both microtubule doublets and triplets with increasing Tau. Furthermore, increasing paclitaxel concentration (up to ΛPtxl=1/1) slightly decreased the average microtubule diameter (by ~1 PF) while increasing Tau concentration (up to Φ3RS=1/2) significantly increased the diameter (by ~2-3 PFs).
  
  
  
  The suppression of Tau-mediated microtubule bundling with increasing paclitaxel is consistent with paclitaxel seeding more, but shorter, microtubules by rapidly exhausting tubulin available for polymerization. Microtubule bundles require the aggregate Tau-Tau attractions along the microtubule length to overcome individual microtubule thermal energies disrupting bundles.
  
  
  
  Investigating MAP-mediated interactions between microtubules (as it relates to in vivo behavior) requires the elimination or minimization of paclitaxel.
authors.affiliation: Department of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology (KAIST), Daejeon 305-701, Republic of Korea.
authors.forename: Myung Chul
authors.initials: MC
authors.lastname: Choi
authors.affiliation: Materials Department, Physics Department, Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, California 93106, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Chung
authors.affiliation: Materials Department, Physics Department, Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, California 93106, USA.
authors.forename: Chaeyeon
authors.initials: C
authors.lastname: Song
authors.affiliation: Neuroscience Research Institute and Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, California 93106, USA.
authors.forename: Herbert P
authors.initials: HP
authors.lastname: Miller
authors.affiliation: Neuroscience Research Institute and Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, California 93106, USA.
authors.forename: E
authors.initials: E
authors.lastname: Kiris
authors.affiliation: Materials Research Laboratory, University of California, Santa Barbara, California 93106, USA.
authors.forename: Youli
authors.initials: Y
authors.lastname: Li
authors.affiliation: Neuroscience Research Institute and Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, California 93106, USA.
authors.forename: Leslie
authors.initials: L
authors.lastname: Wilson
authors.affiliation: Neuroscience Research Institute and Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, California 93106, USA.
authors.forename: Stuart C
authors.initials: SC
authors.lastname: Feinstein
authors.affiliation: Materials Department, Physics Department, Molecular, Cellular, and Developmental Biology Department, University of California, Santa Barbara, California 93106, USA. Electronic address: safinya@mrl.ucsb.edu.
authors.forename: Cyrus R
authors.initials: CR
authors.lastname: Safinya
mesh_terms: D000818:Animals; D002417:Cattle; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017239:Paclitaxel / Q000494:pharmacology*; D053838:Scattering, Small Angle; D014961:X-Ray Diffraction; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016875:tau Proteins; D017239:Paclitaxel
keywords: Microtubule; Paclitaxel; Small-angle X-ray scattering; Tau