Supporting youth mental health with arts-based strategies: a global perspective.

The devastating impact of youth mental health concerns is increasingly evident on a global scale. This crisis calls for innovative solutions that are sufficiently accessible, scalable, and cost-effective to support diverse communities around the world. One such solution involves engagement in the arts: incorporating and building upon existing local resources and cultural practices to bolster youth mental health.

Genetic analysis of the Drosophila ESCRT-III complex protein, VPS24, reveals a novel function in lysosome homeostasis.

The ESCRT pathway is evolutionarily conserved across eukaryotes and plays key roles in a variety of membrane remodeling processes. A new Drosophila mutant recovered in our forward genetic screens for synaptic transmission mutants mapped to the vps24 gene encoding a subunit of the ESCRT-III complex. Molecular characterization indicated a loss of VPS24 function, however the mutant is viable and thus loss of VPS24 may be studied in a developed multicellular organism.

Small heat shock proteins mediate cell-autonomous and -nonautonomous protection in a Drosophila model for environmental-stress-induced degeneration.

Cell and tissue degeneration, and the development of degenerative diseases, are influenced by genetic and environmental factors that affect protein misfolding and proteotoxicity. To better understand the role of the environment in degeneration, we developed a genetic model for heat shock (HS)-stress-induced degeneration in Drosophila This model exhibits a unique combination of features that enhance genetic analysis of degeneration and protection mechanisms involving environmental stress. These include cell-type-specific failure of proteostasis and degeneration in response to global stress, cell-nonautonomous interactions within a simple and accessible network of susceptible cell types, and precise temporal control over the induction of degeneration.

A Distinct Perisynaptic Glial Cell Type Forms Tripartite Neuromuscular Synapses in the Drosophila Adult.

Previous studies of Drosophila flight muscle neuromuscular synapses have revealed their tripartite architecture and established an attractive experimental model for genetic analysis of glial function in synaptic transmission. Here we extend these findings by defining a new Drosophila glial cell type, designated peripheral perisynaptic glia (PPG), which resides in the periphery and interacts specifically with fine motor axon branches forming neuromuscular synapses. Identification and specific labeling of PPG was achieved through cell type-specific RNAi-mediated knockdown (KD) of a glial marker, Glutamine Synthetase 2 (GS2).

The DISABLED protein functions in CLATHRIN-mediated synaptic vesicle endocytosis and exoendocytic coupling at the active zone.

Members of the DISABLED (DAB) family of proteins are known to play a conserved role in endocytic trafficking of cell surface receptors by functioning as monomeric CLATHRIN-associated sorting proteins that recruit cargo proteins into endocytic vesicles. Here, we report a Drosophila disabled mutant revealing a novel role for DAB proteins in chemical synaptic transmission. This mutant exhibits impaired synaptic function, including a rapid activity-dependent reduction in neurotransmitter release and disruption of synaptic vesicle endocytosis.

A tripartite synapse model in Drosophila.

Tripartite (three-part) synapses are defined by physical and functional interactions of glia with pre- and post-synaptic elements. Although tripartite synapses are thought to be of widespread importance in neurological health and disease, we are only beginning to develop an understanding of glial contributions to synaptic function. In contrast to studies of neuronal mechanisms, a significant limitation has been the lack of an invertebrate genetic model system in which conserved mechanisms of tripartite synapse function may be examined through large-scale application of forward genetics and genome-wide genetic tools.

Activity-dependent interactions of NSF and SNAP at living synapses.

As core components of the neurotransmitter release apparatus, SNAREs, NSF and SNAPs mediate fusion of neurotransmitter-filled synaptic vesicles within specialized regions of the presynaptic plasma membrane known as active zones (AZs). The present study combines genetic approaches in Drosophila with biochemical and live-imaging methods to provide new insights into the in vivo behavior and interactions of NSF and SNAP in neurotransmitter release. This work employs a temperature-sensitive (TS) paralytic NSF mutant, comatose, to show that disruption of NSF function results in activity-dependent redistribution of NSF and SNAP to periactive zone (PAZ) regions of the presynaptic plasma membrane and accumulation of protein complexes containing SNAREs, NSF and SNAP.

Molecular mechanisms determining conserved properties of short-term synaptic depression revealed in NSF and SNAP-25 conditional mutants.

Current models of synaptic vesicle trafficking implicate a core complex of proteins comprised of N-ethylmaleimide-sensitive factor (NSF), soluble NSF attachment proteins (SNAPs), and SNAREs in synaptic vesicle fusion and neurotransmitter release. Despite this progress, major challenges remain in establishing the in vivo functions of these proteins and their roles in determining the physiological properties of synapses. The present study employs glutamatergic adult neuromuscular synapses of Drosophila, which exhibit conserved properties of short-term synaptic plasticity with respect to mammalian glutamatergic synapses, to address these issues through genetic analysis.

MAP1 structural organization in Drosophila: in vivo analysis of FUTSCH reveals heavy- and light-chain subunits generated by proteolytic processing at a conserved cleavage site.

The MAP1 (microtubule-associated protein 1) family is a class of microtubule-binding proteins represented by mammalian MAP1A, MAP1B and the recently identified MAP1S. MAP1A and MAP1B are expressed in the nervous system and thought to mediate interactions of the microtubule-based cytoskeleton in neural development and function. The characteristic structural organization of mammalian MAP1s, which are composed of heavy- and light-chain subunits, requires proteolytic cleavage of a precursor polypeptide encoded by the corresponding map1 gene.

Properties of short-term synaptic depression at larval neuromuscular synapses in wild-type and temperature-sensitive paralytic mutants of Drosophila.

The larval neuromuscular synapse of Drosophila serves as an important model for genetic and molecular analysis of synaptic development and function. Further functional characterization of this synapse, as well as adult neuromuscular synapses, will greatly enhance the impact of this model system on our understanding of synaptic transmission. Here we describe a form of short-term synaptic depression observed at larval, but not adult, neuromuscular synapses and explore the underlying mechanisms.

Active zone localization of presynaptic calcium channels encoded by the cacophony locus of Drosophila.

Presynaptic calcium channels play a central role in chemical synaptic transmission by providing the calcium trigger for evoked neurotransmitter release. These voltage-gated calcium channels are composed of a primary structural subunit, alpha1, as well as auxiliary beta and alpha2delta subunits. Our previous genetic, molecular, and functional analysis has shown that the cacophony (cac) gene encodes a primary presynaptic calcium channel alpha1 subunit in Drosophila.

Synaptic calcium-channel function in Drosophila: analysis and transformation rescue of temperature-sensitive paralytic and lethal mutations of cacophony.

Voltage-gated calcium channels play a key role in chemical synaptic transmission by providing the calcium trigger for regulated neurotransmitter release. Genes encoding the primary structural subunit, alpha1, as well as accessory subunits of presynaptic calcium channels have now been identified in a variety of organisms. The cacophony (cac) gene in Drosophila, also known as nightblind A, encodes a voltage-gated calcium-channel alpha1 subunit homologous to vertebrate alpha1 subunits implicated in neurotransmitter release.