Heterogeneous intracellular trafficking dynamics of brain-derived neurotrophic factor complexes in the neuronal soma revealed by single quantum dot tracking

Anke Vermehren-Schmaedick, Wesley Krueger, Thomas Jacob, Damien Ramunno-Johnson, Agnieszka Balkowiec, Keith A. Lidke, Tothu (Tania) Vu

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Accumulating evidence underscores the importance of ligand-receptor dynamics in shaping cellular signaling. In the nervous system, growth factor-activated Trk receptor trafficking serves to convey biochemical signaling that underlies fundamental neural functions. Focus has been placed on axonal trafficking but little is known about growth factor-activated Trk dynamics in the neuronal soma, particularly at the molecular scale, due in large part to technical hurdles in observing individual growth factor-Trk complexes for long periods of time inside live cells. Quantum dots (QDs) are intensely fluorescent nanoparticles that have been used to study the dynamics of ligand-receptor complexes at the plasma membrane but the value of QDs for investigating ligand-receptor intracellular dynamics has not been well exploited. The current study establishes that QD conjugated brain-derived neurotrophic factor (QD-BDNF) binds to TrkB receptors with high specificity, activates TrkB downstream signaling, and allows single QD tracking capability for long recording durations deep within the soma of live neurons. QD-BDNF complexes undergo internalization, recycling, and intracellular trafficking in the neuronal soma. These trafficking events exhibit little time-synchrony and diverse heterogeneity in underlying dynamics that include phases of sustained rapid motor transport without pause as well as immobility of surprisingly long-lasting duration (several minutes). Moreover, the trajectories formed by dynamic individual BDNF complexes show no apparent end destination; BDNF complexes can be found meandering over long distances of several microns throughout the expanse of the neuronal soma in a circuitous fashion. The complex, heterogeneous nature of neuronal soma trafficking dynamics contrasts the reported linear nature of axonal transport data and calls for models that surpass our generally limited notions of nuclear-directed transport in the soma. QD-ligand probes are poised to provide understanding of how the molecular mechanisms underlying intracellular ligand-receptor trafficking shape cell signaling under conditions of both healthy and dysfunctional neurological disease models.

Original languageEnglish (US)
Article numbere95113
JournalPLoS One
Volume9
Issue number4
DOIs
StatePublished - Apr 14 2014

Fingerprint

quantum dots
Quantum Dots
neurotrophins
Brain-Derived Neurotrophic Factor
Carisoprodol
Semiconductor quantum dots
brain
Ligands
receptors
Intercellular Signaling Peptides and Proteins
growth factors
Cell signaling
Neurological Models
trkB Receptor
Axonal Transport
Cell Nucleus Active Transport
Cell Shape
Recycling
cell communication
duration

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Heterogeneous intracellular trafficking dynamics of brain-derived neurotrophic factor complexes in the neuronal soma revealed by single quantum dot tracking. / Vermehren-Schmaedick, Anke; Krueger, Wesley; Jacob, Thomas; Ramunno-Johnson, Damien; Balkowiec, Agnieszka; Lidke, Keith A.; Vu, Tothu (Tania).

In: PLoS One, Vol. 9, No. 4, e95113, 14.04.2014.

Research output: Contribution to journalArticle

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