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Tau proteins cooperatively assemble into cohesive envelopes that protect microtubules against severing enzymes
Siahaan, Valerie ; Braun, Marcus (advisor) ; Middelkoop, Teije Corneel (referee) ; Piliarik, Marek (referee)
Tau is a microtubule-associated protein that is preferentially found in the neuronal axons. In neu- rodegenerative diseases, collectively termed tauopathies, malfunction of tau and its detachment from axonal microtubules, often associated with abnormal phosphorylation of tau, are correlated with axonal degeneration and loss of microtubule mass (Kneynsberg et al., 2017). Tau can protect microtubules from microtubule-degrading enzymes such as katanin (Qiang et al., 2006) and regulate transport by molecular motors along the microtubule (Vershinin et al., 2007; Dixit et al., 2008). However, how tau carries out these regulatory functions is still unclear. Using in vitro re- constitution and TIRF microscopy, we show that tau molecules can bind to microtubules in two distinct modes: either as (i) single tau molecules independently diffusing on the microtubule sur- face, or (ii) cooperatively-bound tau that form a cohesive tau "envelope" enclosing the microtubule lattice (Siahaan et al., 2019; Tanetal., 2019; Siahaan et al., 2022). We found that tau envelope formation alters the spacing of tubulin dimers within the microtubule lattice, where envelope for- mation compacted the underlying lattice, and lattice extension induced tau envelope disassembly (Siahaan et al., 2022). Tau envelopes form a selectively...
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