An image-based RNAi screen identifies the EGFR signaling pathway as a regulator of Imp RNP granules.

Biomolecular condensates have recently retained much attention given that they provide a fundamental mechanism of cellular organization. Among those, cytoplasmic ribonucleoprotein (RNP) granules selectively and reversibly concentrate RNA molecules and regulatory proteins, thus contributing to the spatiotemporal regulation of associated RNAs. Extensive in vitro work has unraveled the molecular and chemical bases of RNP granule assembly.

High-Resolution Live Imaging of Axonal RNP Granules in Drosophila Pupal Brain Explants.

Dynamic and local adjustments of the axonal proteome are observed in response to extracellular cues and achieved via translation of axonally localized mRNAs. To be localized, these mRNAs must be recognized by RNA binding proteins and packaged into higher-order ribonucleoprotein (RNP) granules transported along axonal microtubules via molecular motors. Axonal recruitment of RNP granules is not constitutive, but rather regulated by external signals such as developmental cues, through pathways yet to be identified.

Neuronal ribonucleoprotein granules: Dynamic sensors of localized signals.

Membrane-less organelles, because of their capacity to dynamically, selectively and reversibly concentrate molecules, are very well adapted for local information processing and rapid response to environmental fluctuations. These features are particularly important in the context of neuronal cells, where synapse-specific activation, or localized extracellular cues, induce signaling events restricted to specialized axonal or dendritic subcompartments. Neuronal ribonucleoprotein (RNP) particles, or granules, are nonmembrane bound macromolecular condensates that concentrate specific sets of mRNAs and regulatory proteins, promoting their long-distance transport to axons or dendrites.

The prion-like domain of Drosophila Imp promotes axonal transport of RNP granules in vivo.

Prion-like domains (PLDs), defined by their low sequence complexity and intrinsic disorder, are present in hundreds of human proteins. Although gain-of-function mutations in the PLDs of neuronal RNA-binding proteins have been linked to neurodegenerative disease progression, the physiological role of PLDs and their range of molecular functions are still largely unknown. Here, we show that the PLD of Drosophila Imp, a conserved component of neuronal ribonucleoprotein (RNP) granules, is essential for the developmentally-controlled localization of Imp RNP granules to axons and regulates in vivo axonal remodeling.