Single-molecule analysis of endogenous β-actin mRNA trafficking reveals a mechanism for compartmentalized mRNA localization in axons

De novo protein synthesis in neuronal axons plays important roles in neural circuit formation, maintenance, and disease. Key to the selectivity of axonal protein synthesis is whether an mRNA is present at the right place to be translated, but the mechanisms behind axonal mRNA localization remain poorly understood.

During embryonic nervous system assembly, mRNA localization is precisely regulated in growing axons, affording subcellular autonomy by allowing controlled protein expression in space and time.

How individual molecules move in the cytoplasm holds a trove of information about the biological processes regulating their kinetics.

the contribution of mRNA trafficking to the spatial patterns of mRNA has so far remained elusive.

a modicum of directed transport exists in the axon shaft that is a critical determinant of β-actin mRNA enrichment in the growth cone.

it is highly improbable that β-actin mRNA molecules traverse the length of the axon by diffusion alone, suggesting that at one point they must undergo directed transport.

Directed transport is thus a crucial component of axonal mRNA dynamics.

anterograde and retrograde microtubule-based transport are driven by different microtubule-associated motor proteins: Plus-end–directed kinesins drive anterograde transport, and cytoplasmic dynein drives retrograde transport

different directed transport modes underlie anterograde and retrograde transport.

different numbers of motor proteins attached to cargoes could cause differences in speeds

How motor proteins and their regulators might coordinately control directed mRNA transport in axons is an intriguing avenue for future research that would help us understand further the control of axonal mRNA-localization patterns through mRNA trafficking.