--- res: bibo_abstract: - Elevation of soluble wild-type (WT) tau occurs in synaptic compartments in Alzheimer’s disease. We addressed whether tau elevation affects synaptic transmission at the calyx of Held in slices from mice brainstem. Whole-cell loading of WT human tau (h-tau) in presynaptic terminals at 10–20 µM caused microtubule (MT) assembly and activity-dependent rundown of excitatory neurotransmission. Capacitance measurements revealed that the primary target of WT h-tau is vesicle endocytosis. Blocking MT assembly using nocodazole prevented tau-induced impairments of endocytosis and neurotransmission. Immunofluorescence imaging analyses revealed that MT assembly by WT h-tau loading was associated with an increased MT-bound fraction of the endocytic protein dynamin. A synthetic dodecapeptide corresponding to dynamin 1-pleckstrin-homology domain inhibited MT-dynamin interaction and rescued tau-induced impairments of endocytosis and neurotransmission. We conclude that elevation of presynaptic WT tau induces de novo assembly of MTs, thereby sequestering free dynamins. As a result, endocytosis and subsequent vesicle replenishment are impaired, causing activity-dependent rundown of neurotransmission.@eng bibo_authorlist: - foaf_Person: foaf_givenName: Tetsuya foaf_name: Hori, Tetsuya foaf_surname: Hori - foaf_Person: foaf_givenName: Kohgaku foaf_name: Eguchi, Kohgaku foaf_surname: Eguchi foaf_workInfoHomepage: http://www.librecat.org/personId=2B7846DC-F248-11E8-B48F-1D18A9856A87 orcid: 0000-0002-6170-2546 - foaf_Person: foaf_givenName: Han Ying foaf_name: Wang, Han Ying foaf_surname: Wang - foaf_Person: foaf_givenName: Tomohiro foaf_name: Miyasaka, Tomohiro foaf_surname: Miyasaka - foaf_Person: foaf_givenName: Laurent foaf_name: Guillaud, Laurent foaf_surname: Guillaud - foaf_Person: foaf_givenName: Zacharie foaf_name: Taoufiq, Zacharie foaf_surname: Taoufiq - foaf_Person: foaf_givenName: Satyajit foaf_name: Mahapatra, Satyajit foaf_surname: Mahapatra - foaf_Person: foaf_givenName: Hiroshi foaf_name: Yamada, Hiroshi foaf_surname: Yamada - foaf_Person: foaf_givenName: Kohji foaf_name: Takei, Kohji foaf_surname: Takei - foaf_Person: foaf_givenName: Tomoyuki foaf_name: Takahashi, Tomoyuki foaf_surname: Takahashi bibo_doi: 10.7554/eLife.73542 bibo_volume: 11 dct_date: 2022^xs_gYear dct_identifier: - UT:000876231600001 dct_isPartOf: - http://id.crossref.org/issn/2050-084X dct_language: eng dct_publisher: eLife Sciences Publications@ dct_title: Microtubule assembly by tau impairs endocytosis and neurotransmission via dynamin sequestration in Alzheimer's disease synapse model@ fabio_hasPubmedId: '35471147 ' ...