Abstract
Tau is a major microtubule-associated protein which induces bundling and stabilization of axonal microtubules (MTs). To investigate the interaction of tau with MTs in living cells, we expressed GFP-tau fusion protein in cultured Xenopus embryo neurons and performed time-lapse imaging of tau-labeled MTs. Tau uniformly labeled individual MTs regardless of their assembly/disassembly status and location along the axon. Photobleaching experiments indicated that interaction of tau with MTs is very dynamic, with a half-time of fluorescence recovery of the order of 3 seconds. Treatment of cells with taxol, a drug that suppresses MT dynamics, rapidly induced detachment of tau from MTs. Although binding of tau to straight MTs was uniform, there was a heightened concentration of tau at the sites of high MT curvature. Our results suggest that dynamic interaction of tau with MTs may modify local mechanical properties of individual MTs and play a crucial role in the remodeling of the MT cytoskeleton during neuronal plasticity.
Highlights
Neuronal microtubules (MTs) are essential for neurite extension, axonal guidance, and communication between the cell body and neuronal processes
Using a combination of time-lapse microscopy and a photobleaching method, we examined the dynamics of tau association with MTs in living cells
We report that association of tau with individual MTs in neurons is very rapid, does not depend on MT location along the axon, and is strongly affected by MT curvature
Summary
Neuronal microtubules (MTs) are essential for neurite extension, axonal guidance, and communication between the cell body and neuronal processes. Mice deficient in tau are essentially normal (Harada et al, 1994), knockout of both tau and MAP1B leads to serious neuronal defects (Takei et al, 2000), suggesting functional redundancy between these (and, perhaps other) MAPs. Interestingly, in humans, mutations in tau linked to some neurodegenerative diseases reduce the ability of tau to promote MT assembly (D’Souza et al, 1999; Hasegawa et al, 1999). In humans, mutations in tau linked to some neurodegenerative diseases reduce the ability of tau to promote MT assembly (D’Souza et al, 1999; Hasegawa et al, 1999) These data predict that tau-induced stabilization of the MT cytoskeleton is essential for proper development of nerve processes
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