Tau regulates the attachment/detachment but not the speed of motors in microtubule-dependent transport of single vesicles and organelles.
We have performed a real time analysis of fluorescence-tagged vesicle and mitochondria movement in living CHO cells transfected with microtubule-associated protein tau or its microtubule-binding domain. tau does not alter the speed of moving vesicles, but it affects the frequencies of attachment and detachment to the microtubule tracks. Thus, tau decreases the run lengths both for plus-end and minus-end directed motion to an equal extent. Reversals from minus-end to plus-end directed movement of single vesicles are strongly reduced by tau, but reversals in the opposite direction (plus to minus) are not. Analogous effects are observed with the transport of mitochondria and even with that of vimentin intermediate filaments. The net effect is a directional bias in the minus-end direction of microtubules which leads to the retraction of mitochondria or vimentin IFs towards the cell center. The data suggest that tau can control intracellular trafficking by affecting the attachment and detachment cycle of the motors, in particular by reducing the attachment of kinesin to microtubules, whereas the movement itself is unaffected.
Trinczek
B
B
Max-Planck Unit for Structural Molecular Biology, Notkestrasse 85, D-22607 Hamburg, Germany. trinczek@mpasmb.desy.de
Ebneth
A
A
Mandelkow
E M
EM
Mandelkow
E
E
D000818:Animals; D001665:Binding Sites; D001693:Biological Transport, Active; D016466:CHO Cells; D006224:Cricetinae; D005089:Exocytosis; D005456:Fluorescent Dyes; D006801:Humans; D007382:Intermediate Filaments / Q000502:physiology; D016547:Kinesins / Q000502:physiology; D008870:Microtubules / Q000502:physiology*; D020409:Molecular Motor Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009068:Movement; D015388:Organelles / Q000502:physiology; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D014162:Transfection; D014746:Vimentin / Q000502:physiology; D016875:tau Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
D005456:Fluorescent Dyes; D020409:Molecular Motor Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; D014746:Vimentin; D016875:tau Proteins; D016547:Kinesins