Peripheral glia and neurons jointly regulate activity-induced synaptic remodeling at the Drosophila neuromuscular junction.

In the nervous system, reliable communication depends on the ability of neurons to adaptively remodel their synaptic structure and function in response to changes in neuronal activity. While neurons are the main drivers of synaptic plasticity, glial cells are increasingly recognized for their roles as active modulators. However, the underlying molecular mechanisms remain unclear.

Identification of secretory autophagy as a mechanism modulating activity-induced synaptic remodeling.

The ability of neurons to rapidly remodel their synaptic structure and strength in response to neuronal activity is highly conserved across species and crucial for complex brain functions. However, mechanisms required to elicit and coordinate the acute, activity-dependent structural changes across synapses are not well understood, as neurodevelopment and structural plasticity are tightly linked. Here, using an RNAi screen in against genes affecting nervous system functions in humans, we uncouple cellular processes important for synaptic plasticity and synapse development.

Identification of secretory autophagy as a novel mechanism modulating activity-induced synaptic remodeling.

The ability of neurons to rapidly remodel their synaptic structure and strength in response to neuronal activity is highly conserved across species and crucial for complex brain functions. However, mechanisms required to elicit and coordinate the acute, activity-dependent structural changes across synapses are not well understood. Here, using an RNAi screen in against genes affecting nervous system functions in humans, we uncouple cellular processes important for synaptic plasticity from synapse development.

Inhibition, but not excitation, recovers from partial cone loss with greater spatiotemporal integration, synapse density, and frequency.

Neural circuits function in the face of changing inputs, either caused by normal variation in stimuli or by cell death. To maintain their ability to perform essential computations with partial inputs, neural circuits make modifications. Here, we study the retinal circuit's responses to changes in light stimuli or in photoreceptor inputs by inducing partial cone death in the mature mouse retina.

Lysine acetylation regulates the interaction between proteins and membranes.

Lysine acetylation regulates the function of soluble proteins in vivo, yet it remains largely unexplored whether lysine acetylation regulates membrane protein function. Here, we use bioinformatics, biophysical analysis of recombinant proteins, live-cell fluorescent imaging and genetic manipulation of Drosophila to explore lysine acetylation in peripheral membrane proteins. Analysis of 50 peripheral membrane proteins harboring BAR, PX, C2, or EHD membrane-binding domains reveals that lysine acetylation predominates in membrane-interaction regions.

Impact of Photoreceptor Loss on Retinal Circuitry.

Our sense of sight relies on photoreceptors, which transduce photons into the nervous system's electrochemical interpretation of the visual world. These precious photoreceptors can be disrupted by disease, injury, and aging. Once photoreceptors start to die, but before blindness occurs, the remaining retinal circuitry can withstand, mask, or exacerbate the photoreceptor deficit and potentially be receptive to newfound therapies for vision restoration.

Activity-Induced Synaptic Structural Modifications by an Activator of Integrin Signaling at the Neuromuscular Junction.

Activity-induced synaptic structural modification is crucial for neural development and synaptic plasticity, but the molecular players involved in this process are not well defined. Here, we report that a protein named Shriveled (Shv) regulates synaptic growth and activity-dependent synaptic remodeling at the neuromuscular junction. Depletion of Shv causes synaptic overgrowth and an accumulation of immature boutons.

Phosphorylation of Synaptojanin Differentially Regulates Endocytosis of Functionally Distinct Synaptic Vesicle Pools.

Unlabelled: The rapid replenishment of synaptic vesicles through endocytosis is crucial for sustaining synaptic transmission during intense neuronal activity. Synaptojanin (Synj), a phosphoinositide phosphatase, is known to play an important role in vesicle recycling by promoting the uncoating of clathrin following synaptic vesicle uptake. Synj has been shown to be a substrate of the minibrain (Mnb) kinase, a fly homolog of the dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A); however, the functional impacts of Synj phosphorylation by Mnb are not well understood.

Maintenance of Stem Cell Niche Integrity by a Novel Activator of Integrin Signaling.

Stem cells depend critically on the surrounding microenvironment, or niche, for their maintenance and self-renewal. While much is known about how the niche regulates stem cell self-renewal and differentiation, mechanisms for how the niche is maintained over time are not well understood. At the apical tip of the Drosophila testes, germline stem cells (GSCs) and somatic stem cells share a common niche formed by hub cells.

Non-coding RNAs derived from an alternatively spliced REST transcript (REST-003) regulate breast cancer invasiveness.

RE1-Silencing Transcription factor (REST) has a well-established role in regulating transcription of genes important for neuronal development. Its role in cancer, though significant, is less well understood. We show that REST downregulation in weakly invasive MCF-7 breast cancer cells converts them to a more invasive phenotype, while REST overexpression in highly invasive MDA-MB-231 cells suppresses invasiveness.