Structure of an Arc-ane virus-like capsid.

Recent findings unveil a viral-like mechanism for the transmission of synaptic plasticity signals involving the activity-regulated cytoskeleton-associated protein (Arc). Arc forms capsid-like particles that package RNA and are transported across synapses. Here Erlendsson et al.

Retrovirus-like Gag Protein Arc1 Binds RNA and Traffics across Synaptic Boutons.

Arc/Arg3.1 is required for synaptic plasticity and cognition, and mutations in this gene are linked to autism and schizophrenia. Arc bears a domain resembling retroviral/retrotransposon Gag-like proteins, which multimerize into a capsid that packages viral RNA.

Getting mRNA-Containing Ribonucleoprotein Granules Out of a Nuclear Back Door.

A pivotal feature of long-lasting synaptic plasticity is the localization of RNAs and the protein synthesis machinery at synaptic sites. How and where ribonucleoprotein (RNP) transport granules that support this synthetic activity are formed is of fundamental importance. The prevailing model poses that the nuclear pore complex (NPC) is the sole gatekeeper for transit of cellular material in and out of the nucleus.

A Tale of Two Inputs.

In this issue of Neuron, Newman et al. (2017) image calcium events at single synapses of unanesthetized Drosophila larvae. Synaptic plasticity and homeostatic regulation of synapses is established to be input specific.

Lamin Mutations Accelerate Aging via Defective Export of Mitochondrial mRNAs through Nuclear Envelope Budding.

Defective RNA metabolism and transport are implicated in aging and degeneration [1, 2], but the underlying mechanisms remain poorly understood. A prevalent feature of aging is mitochondrial deterioration [3]. Here, we link a novel mechanism for RNA export through nuclear envelope (NE) budding [4, 5] that requires A-type lamin, an inner nuclear membrane-associated protein, to accelerated aging observed in Drosophila LaminC (LamC) mutations.

This bud's for you: mechanisms of cellular nucleocytoplasmic trafficking via nuclear envelope budding.

The nuclear envelope (NE) physically separates the cytoplasmic and nuclear compartments. While this barrier provides advantages, it also presents a challenge for the nuclear export of large ribonucleoprotein (RNP) complexes. Decades-old dogma holds that all such border-crossing is via the nuclear pore complex (NPC).

Extracellular vesicles round off communication in the nervous system.

Functional neural competence and integrity require interactive exchanges among sensory and motor neurons, interneurons and glial cells. Recent studies have attributed some of the tasks needed for these exchanges to extracellular vesicles (such as exosomes and microvesicles), which are most prominently involved in shuttling reciprocal signals between myelinating glia and neurons, thus promoting neuronal survival, the immune response mediated by microglia, and synapse assembly and plasticity. Such vesicles have also been identified as important factors in the spread of neurodegenerative disorders and brain cancer.

Nucleus to Synapse Nesprin1 Railroad Tracks Direct Synapse Maturation through RNA Localization.

An important mechanism underlying synapse development and plasticity is the localization of mRNAs that travel from the nucleus to synaptic sites. Here we demonstrate that the giant nuclear-associated Nesprin1 (dNesp1) forms striated F-actin-based filaments, which we dubbed "railroad tracks," that span from muscle nuclei to postsynaptic sites at the neuromuscular junction in Drosophila. These railroad tracks specifically wrap around immature boutons formed during development and in response to electrical activity.

Glial wingless/Wnt regulates glutamate receptor clustering and synaptic physiology at the Drosophila neuromuscular junction.

Glial cells are emerging as important regulators of synapse formation, maturation, and plasticity through the release of secreted signaling molecules. Here we use chromatin immunoprecipitation along with Drosophila genomic tiling arrays to define potential targets of the glial transcription factor Reversed polarity (Repo). Unexpectedly, we identified wingless (wg), a secreted morphogen that regulates synaptic growth at the Drosophila larval neuromuscular junction (NMJ), as a potential Repo target gene.

Exosomes go with the Wnt.

Exosomes, small secreted microvesicles, are implicated in intercellular communication in diverse cell types, transporting protein, lipid and nucleic acid cargo that impact the physiology of recipient cells. Besides the signaling function of exosomes they also serve as a mechanism to dispose obsolete cellular material. Particularly exciting is the involvement of exosomal communication in the nervous system, as this has important implications for brain development and function.

Torsin mediates primary envelopment of large ribonucleoprotein granules at the nuclear envelope.

A previously unrecognized mechanism through which large ribonucleoprotein (megaRNP) granules exit the nucleus is by budding through the nuclear envelope (NE). This mechanism is akin to the nuclear egress of herpes-type viruses and is essential for proper synapse development. However, the molecular machinery required to remodel the NE during this process is unknown.

Regulation of postsynaptic retrograde signaling by presynaptic exosome release.

Retrograde signals from postsynaptic targets are critical during development and plasticity of synaptic connections. These signals serve to adjust the activity of presynaptic cells according to postsynaptic cell outputs and to maintain synaptic function within a dynamic range. Despite their importance, the mechanisms that trigger the release of retrograde signals and the role of presynaptic cells in this signaling event are unknown.

Vesiclepedia: a compendium for extracellular vesicles with continuous community annotation.

Extracellular vesicles (EVs) are membraneous vesicles released by a variety of cells into their microenvironment. Recent studies have elucidated the role of EVs in intercellular communication, pathogenesis, drug, vaccine and gene-vector delivery, and as possible reservoirs of biomarkers. These findings have generated immense interest, along with an exponential increase in molecular data pertaining to EVs.

Integration of a retrograde signal during synapse formation by glia-secreted TGF-β ligand.

Glial cells are crucial regulators of synapse formation, elimination, and plasticity [1, 2]. In vitro studies have begun to identify glial-derived synaptogenic factors [1], but neuron-glia signaling events during synapse formation in vivo remain poorly defined. The coordinated development of pre- and postsynaptic compartments at the Drosophila neuromuscular junction (NMJ) depends on a muscle-secreted retrograde signal, the TGF-β/BMP Glass bottom boat (Gbb) [3, 4].

Nuclear envelope budding enables large ribonucleoprotein particle export during synaptic Wnt signaling.

Localized protein synthesis requires assembly and transport of translationally silenced ribonucleoprotein particles (RNPs), some of which are exceptionally large. Where in the cell such large RNP granules first assemble was heretofore unknown. We previously reported that during synapse development, a fragment of the Wnt-1 receptor, DFrizzled2, enters postsynaptic nuclei where it forms prominent foci.

Inhibitory control of synaptic and behavioral plasticity by octopaminergic signaling.

Adrenergic receptors and their ligands are important regulators of synaptic plasticity and metaplasticity, but the exact mechanisms underlying their action are still poorly understood. Octopamine, the invertebrate homolog of mammalian adrenaline or noradrenaline, plays important roles in modulating behavior and synaptic functions. We previously uncovered an octopaminergic positive-feedback mechanism to regulate structural synaptic plasticity during development and in response to starvation.

Wnt signaling in neuromuscular junction development.

Wnt proteins are best known for their profound roles in cell patterning, because they are required for the embryonic development of all animal species studied to date. Besides regulating cell fate, Wnt proteins are gaining increasing recognition for their roles in nervous system development and function. New studies indicate that multiple positive and negative Wnt signaling pathways take place simultaneously during the formation of vertebrate and invertebrate neuromuscular junctions.

Mechanism of evenness interrupted (Evi)-exosome release at synaptic boutons.

Wnt signaling plays critical roles during synaptic development and plasticity. However, the mechanisms by which Wnts are released and travel to target cells are unresolved. During synaptic development, the secretion of Drosophila Wnt1, Wingless, requires the function of Evenness Interrupted (Evi)/Wls, a Wingless-binding protein that is secreted along with Wingless at the neuromuscular junction.

From synapse to nucleus and back again--communication over distance within neurons.

How do neurons integrate intracellular communication from synapse to nucleus and back? Here we briefly summarize aspects of this topic covered by a symposium at Neuroscience 2011. A rich repertoire of signaling mechanisms link both dendritic terminals and axon tips with neuronal soma and nucleus, using motor-dependent transport machineries to traverse the long intracellular distances along neuronal processes. Activation mechanisms at terminals include localized translation of dendritic or axonal RNA, proteolytic cleavage of receptors or second messengers, and differential phosphorylation of signaling moieties.

Wnt signaling during synaptic development and plasticity.

The formation of synaptic connections requires a dialogue between pre and postsynaptic cells to coordinate the assembly of the presynaptic release machinery and the postsynaptic receptive complexes. Signaling molecules of the Wnt family of proteins are central to this trans-synaptic dialogue. At the neuromuscular junction and central synapses, Wnts promote synaptic assembly by signaling to the developing pre and postsynaptic compartments.

Autoregulatory and paracrine control of synaptic and behavioral plasticity by octopaminergic signaling.

Adrenergic signaling has important roles in synaptic plasticity and metaplasticity. However, the underlying mechanisms of these functions remain poorly understood. We investigated the role of octopamine, the invertebrate counterpart of adrenaline and noradrenaline, in synaptic and behavioral plasticity in Drosophila.

Preparation of late Drosophila embryonic fillets.

Beyond the age of ~15 h (at 25°C), Drosophila embryos become impenetrable to aqueous fixatives and staining methods as a result of cuticle deposition. This problem can be overcome using flat or fillet preparations, as described in this protocol.

Preparation of early Drosophila embryonic fillets (before cuticle deposition).

This article describes the dissection of early Drosophila embryos to generate flat or fillet preparations. For the procedure, a modified chamber or well is designed using glass slides and sealant. Embryos are dissected by removing the chorionic (outer) membrane (performed outside the chamber) and then removing the vitelline (inner) membrane (performed inside the chamber and under saline).

The role of Drosophila Lamin C in muscle function and gene expression.

The inner side of the nuclear envelope (NE) is lined with lamins, a meshwork of intermediate filaments that provides structural support for the nucleus and plays roles in many nuclear processes. Lamins, classified as A- or B-types on the basis of biochemical properties, have a conserved globular head, central rod and C-terminal domain that includes an Ig-fold structural motif. In humans, mutations in A-type lamins give rise to diseases that exhibit tissue-specific defects, such as Emery-Dreifuss muscular dystrophy.