To characterize axonal TDP-43 transport in human neurons and identify motor proteins associated with its movement.
Approach:
Neuronal model: The study examined fluorescently labeled TDP-43 in neurons derived from the H9 human embryonic stem-cell line.
Transport analysis: Live-cell imaging and segmental trajectory analysis assessed TDP-43 movement alongside Rab5, synaptophysin, and amyloid precursor protein.
Motor-protein interactions: Biochemical assays and proximity ligation analyses examined TDP-43 associations with axonal transport machinery.
Key Findings:
TDP-43 showed processive anterograde axonal movement, with kinetics comparable to vesicular cargoes.
TDP-43 was associated with both anterograde and retrograde transport machinery, consistent with bidirectional movement.
TDP-43 interacted with kinesin-1 isoforms KIF5A, KIF5B, and KIF5C via KLC1, and with kinesin-3 family member KIF1A.
Interpretation:
The authors propose that TDP-43-containing ribonucleoprotein structures may use a flexible, multi-motor transport system to support mRNA delivery across axonal compartments.
Limitations:
The provided context does not report study limitations.
The provided context does not include the full methods or results, including sample sizes and quantitative findings.
by Monica Feole, Victorio M. Pozo Devoto, Neda Dragišić, Maria Čarna, Katja Klosterman, Clara Limbaek-Stokin, Giancarlo Forte, Kenneth L. Moya, Richard A. Smith, Clive N. Svendsen, Gorazd B. Stokin
The federal settlement resolves allegations of unlawful controlled substance prescribing and absent patient records and restricts future DEA registration for certain controlled substances.
