T-complex protein 1-ring complex enhances retrograde axonal transport by modulating tau phosphorylation

Area of Science:

• Neuroscience
• Cell Biology
• Molecular Biology

Background:

• The T-complex protein (TCP) 1-ring complex (TRiC) is known for neuroprotection in Huntington's disease by clearing mutant Huntingtin.
• Its role in axonal transport in wild-type neurons remains unexplored.

Purpose of the Study:

• To investigate the impact of TRiC on the retrograde axonal transport of brain-derived neurotrophic factor (BDNF) in wild-type neurons.
• To elucidate the molecular mechanisms underlying TRiC's influence on axonal transport.

Main Methods:

• Examined BDNF retrograde axonal transport in neurons with altered TRiC subunit expression.
• Utilized tau knockout mouse neurons to assess tau dependency.
• Investigated the role of cyclin-dependent kinase 5 (CDK5)/p35 and tau phosphorylation (ptau) in TRiC-mediated transport.

Main Results:

• Expression of a single TRiC subunit significantly enhanced BDNF retrograde axonal transport velocity and reduced pauses.
• TRiC's effect was dependent on endogenous tau expression.
• TRiC positively regulated CDK5/p35, increasing ptau levels and causing tau detachment from microtubules.

Conclusions:

• TRiC enhances retrograde axonal transport of BDNF in a tau-dependent manner.
• TRiC-mediated tau phosphorylation is a key mechanism influencing axonal transport dynamics.
• TRiC plays a significant role in regulating neuronal transport pathways.