The Role of the Axon Initial Segment and Tau Modifications in Axosomatic Tau Distribution.
- Resource Type
- Theses
- Authors
- Kneynsberg, Andrew
- Source
- Dissertation Abstracts International; Dissertation Abstract International; 79-09B(E).
- Subject
- Neurosciences
Molecular biology
Health sciences
- Language
- English
Summary: Knockdown of TRIM46 is sufficient to allow somatic diffusion of axonal tau into the somata of neurons and reduce the relative axonal enrichment of tau. Knockdown of AnkG does not change tau localization or axo-somatic distribution. Immunoprecipitation and mass spectrometry was used to characterize this connection between tau and TRIM46, but we conclude that tau and TRIM46 do not interact directly. Instead, we identified TRIM46 interactions with several microtubule-associated and actin-associated proteins supporting an integral role in maintenance of the AIS cytoarchitecture. We propose that the tight regulation of microtubule organization in the AIS by TRIM46 prevents somatic diffusion of tau, and tau modifications that disrupt its interactions with microtubules contributes to axosomatic mislocalization.