An N-terminal motif unique to primate tau enables differential protein–protein interactions

Abstract

Compared with other mammalian species, humans are particularly susceptible to taumediated neurodegenerative disorders. Differential interactions of the tau protein with other proteins are critical for mediating tau's physiological functions as well as tauassociated pathological processes. Primate tau harbors an 11-amino-acid-long motif in its Nterminal region (residues 18-28), which is not present in non-primate species and whose function is unknown. Here, we used deletion mutagenesis to remove this sequence region from the longest human tau isoform, followed by glutathione-S transferase (GST) pulldown assays paired with isobaric tags for relative and absolute quantitation (iTRAQ) multiplex labeling, a quantitative method to measure protein abundance by mass spectrometry.

Neuronal MAP kinase p38α inhibits c-Jun N-terminal kinase to modulate anxiety-related behaviour

“…gRNA template oligos were inserted into pX458 (Addgene; 48138) by oligocloning. 293 T cells were transfected using polyethyleneimine (PEI) 55 . 16 hours post-transfection, cells were trypsinized, washed with PBS and resuspended in FACS sorting buffer (2%FCS, 2 mM EDTA, PBS pH 7.4).…”

Dendritic Tau in Alzheimer’s Disease

“…An alternative mechanism of axonal tau enrichment has been proposed with the identification of its interaction with Annexin A2 in the distal part of the axon, providing a sink for directional distribution of tau (Gauthier-Kemper et al, 2011). Interestingly, Annexin A5, another member of the Annexin family, also binds to tau (Stefanoska et al, 2018). It remains to be shown whether similar interaction partners of tau reside in other neuronal compartments, including the post-synapse, to provide additional local sinks.…”

Tau filaments in neurodegenerative diseases

“…of Tau and annexins may help to explain the axonal localization of tau [13]. Exon 1 contains a primate-specific sequence between residues 18 and 28 of human Tau that has been proposed to mediate interactions with neuronal proteins [14]. The PXXP motifs in the prolinerich region of Tau mediate recognition of SH3 domaincontaining proteins of the Src family of nonreceptor tyrosine kinases, such as Fyn [15].…”