A direct Force Measurement Reveals that Human Microtubule-Associated-Protein tau Modulates the Interactions Betweem Microtubules in an Isoform Dependent Manner

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. A variety of microtubule-associated-proteins (MAPs) bind to tubulin subunits and regulate microtubule dynamics, although the process in which this occurs is not well understood. In mature neurons MAP tau promotes MT assembly while in developing neurons MAP tau also plays a critical role in axonogensis [1]. Furthermore, aberrant tau function has been implicated in numerous neurodegenerative diseases, such as Alzheimer's, Pick's, and supranuclear palsy. Understanding the interactions between MAP tau and MTs will be critical in further elucidating the role that MAP tau plays in neurodegenerative diseases. We examined the effects of the human MAP tau on the assembled structure of taxol-stabilized MTs under osmotic pressure (mimicking the crowded environment of axonal neurons) using synchrotron small angle x-ray scattering (SAXS) and binding assays [2, 3]. Previous work had shown that MAP tau isoforms regulate the distribution of protofilament numbers in MTs resulting in an increase in the average MT radius with increasing tau [4]. Significantly, the pressure-tau concentration phase diagram (using the SAXS-osmotic pressure technique) reveal that tau does indeed modify the interactions between MTs in an isoform dependent manner.Supported by DOE DE-FG02-06ER46314, NSF DMR-0803103, NIH NS35010, NIH NS13560.1. B. Esmaeli-Azad, J. H. McCarty, and S. C. Feinstein. J. Cell Sci. 107; 869 (1994).2. V. A. Parsegian, R.P. Rand, and D.C. Rau. Methods Enzymol. 259; 43 (1995).3. D.J. Needleman et al. Phys. Rev. Lett. 93; 198104 (2004).4. M.C. Choi, U. Raviv et al. Biophys. J. 97; 519 (2009).