CUED Publications database

Paradoxical relationships between active transport and global protein distributions in neurons

Bellotti, A and Murphy, J and Lin, L and Petralia, R and Wang, YX and Hoffman, D and O'Leary, T (2021) Paradoxical relationships between active transport and global protein distributions in neurons. Biophysical Journal, 120. pp. 2085-2101. ISSN 0006-3495

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Neural function depends on continual synthesis and targeted trafficking of intracellular components, including ion channel proteins. Many kinds of ion channels are trafficked over long distances to specific cellular compartments. This raises the question of whether cargo is directed with high specificity during transit or whether cargo is distributed widely and sequestered at specific sites. We addressed this question by experimentally measuring transport and expression densities of Kv4.2, a voltage-gated transient potassium channel that exhibits a specific dendritic expression that increases with distance from the soma and little or no functional expression in axons. In over 500 h of quantitative live imaging, we found substantially higher densities of actively transported Kv4.2 subunits in axons as opposed to dendrites. This paradoxical relationship between functional expression and traffic density supports a model—commonly known as the sushi belt model—in which trafficking specificity is relatively low and active sequestration occurs in compartments where cargo is expressed. In further support of this model, we find that kinetics of active transport differs qualitatively between axons and dendrites, with axons exhibiting strong superdiffusivity, whereas dendritic transport resembles a weakly directed random walk, promoting mixing and opportunity for sequestration. Finally, we use our data to constrain a compartmental reaction-diffusion model that can recapitulate the known Kv4.2 density profile. Together, our results show how nontrivial expression patterns can be maintained over long distances with a relatively simple trafficking mechanism and how the hallmarks of a global trafficking mechanism can be revealed in the kinetics and density of cargo.

Item Type: Article
Divisions: Div F > Control
Depositing User: Cron Job
Date Deposited: 18 Jun 2021 22:53
Last Modified: 05 Aug 2021 05:17
DOI: 10.1016/j.bpj.2021.02.048