首页 | 本学科首页   官方微博 | 高级检索  
   检索      


Tau Protein Diffuses along the Microtubule Lattice
Authors:Maike H Hinrichs  Avesta Jalal  Bernhard Brenner  Eckhard Mandelkow  Satish Kumar  Tim Scholz
Institution:From the Institute for Molecular and Cell Physiology, Hannover Medical School, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany.;the §German Center for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases, 53175 Bonn, Germany, and ;the CAESAR Research Center, Ludwig-Erhard-Allee 2, 53175 Bonn, Germany
Abstract:Current models for the intracellular transport of Tau protein suggest motor protein-dependent co-transport with microtubule fragments and diffusion of Tau in the cytoplasm, whereas Tau is believed to be stationary while bound to microtubules and in equilibrium with free diffusion in the cytosol. Observations that members of the microtubule-dependent kinesin family show Brownian motion along microtubules led us to hypothesize that diffusion along microtubules could also be relevant in the case of Tau. We used single-molecule total internal reflection fluorescence microscopy to probe for diffusion of individual fluorescently labeled Tau molecules along microtubules. This allowed us to avoid the problem that microtubule-dependent diffusion could be masked by excess of labeled Tau in solution that might occur in in vivo overexpression experiments. We found that approximately half of the individually detected Tau molecules moved bidirectionally along microtubules over distances up to several micrometers. Diffusion parameters such as diffusion coefficient, interaction time, and scanned microtubule length did not change with Tau concentration. Tau binding and diffusion along the microtubule lattice, however, were sensitive to ionic strength and pH and drastically reduced upon enzymatic removal of the negatively charged C termini of tubulin. We propose one-dimensional Tau diffusion guided by the microtubule lattice as one possible additional mechanism for Tau distribution. By such one-dimensional microtubule lattice diffusion, Tau could be guided to both microtubule ends, i.e. the sites where Tau is needed during microtubule polymerization, independently of directed motor-dependent transport. This could be important in conditions where active transport along microtubules might be compromised.
Keywords:Alzheimer Disease  MAPs  Microtubules  Neurodegenerative Diseases  Single-molecule Biophysics  E-hook  One-dimensional Diffusion
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号