Fig. 3

Spastin domain structure, and proposed mechanism of Tau mediated microtubule loss. a Domain structure of spastin. Spastin contains four main domains: TM, transmembrane domain; MIT, microtubule interacting and transport domain, MTBD, microtubule binding domain; and AAA, ATPase associated with various cellular activities domain. Adapted from [56, 60]. b Severing of microtubules by spastin and subsequent disassembly. MTs are fluorescently labeled (Atto488) and stabilized by taxol. Yellow arrowheads indicate areas where microtubules are severed by spastin. Figure by courtesy of G. Woehlke (Tech. Univ. Munich), adapted from [17]. For movies of spastin-induced severing of microtubules see [17]. c Model of Tau dependent spastin mediated severing of microtubules: (1) Missorted Tau induces translocation of TTLL6 to dendritic microtubules. (2) Tau detaches from microtubules (i.e. has a reduced dwell time on microtubules, possibly as a result of increased phosphorylation by MARK). (3) TTLL6 executes polyglutamylation of microtubules which triggers the activation of spastin and severing of microtubules