Biology subjects

Chuang, C.-F.

Publications and source records attributed to Chuang, C.-F..

5 recordsLinked to original sources

bioRxiv2026

A JNK-interacting protein 1 acts across the midline to mediate synaptic localization of the SARM1 calcium-signaling scaffold protein for asymmetric neuronal fate choice

The Caenorhabditis elegans AWC olfactory neuron pair specifies asymmetric subtypes, AWCOFF and AWCON, through stochastic and coordinated cell signaling events. UNC-104/kinesin-3 (KIF1A) and UNC-116/kinesin-1 motor proteins act in the AWCON cell to regulate the synaptic localization of the TIR-1/SARM1-assembled calcium signaling complex in the AWCOFF cell to promote AWCOFF. However, the molecular mechanism in the AWCON cell that acts non-cell autonomously to control synaptic TIR-1 calcium signaling to promote AWCOFF remains unclear. Here, we show that JIP-1, a conserved c-Jun N-terminal kinase (JNK)-interacting protein 1, mediates the synaptic localization of TIR-1 in the AWC axon to specify the AWCOFF subtype. A jip-1 loss-of-function mutant, identified from an unbiased forward genetic screen, has reduced localization of TIR-1 at synapses in the AWC axon and accumulation of TIR-1 in the AWC cell body. jip-1 mutants significantly enhance the 2AWCON phenotype of a hypomorphic tir-1 mutant. JIP-1, like UNC-104 and UNC-116, mainly acts non-cell autonomously in AWCON to specify the AWCOFF subtype. Our findings provide mechanistic insights into how cell-specific Ca2+ signaling proteins, such as TIR-1, target synaptic regions via intercellular signaling to promote neuronal diversification.

developmental biology↗

bioRxiv2026

An apical junction protein antagonizes mechanosensitive calcium signaling to establish stochastic choices of olfactory neuron subtypes

Mechanical forces regulate brain development and left-right body patterning. However, the role of mechanical signaling in brain lateralization remains unclear. In Caenorhabditis elegans, the left and right AWC olfactory neurons communicate via a gap junction network to stochastically differentiate into the default AWCOFF and induced AWCON subtypes. SLO BK potassium channels, SLO-1 and SLO-2, act redundantly to inhibit a calcium-regulated protein kinase pathway in the specification of the AWCON subtype. Here, we identified a role for AJM-1 (apical junction molecule 1) in promoting AWCON from an unbiased forward genetic screen for mutants that suppress the slo-1(gf) 2AWCON phenotype. AJM-1 is located at three distinct tight junctions between amphid neurons (including AWC) and sheath glia, sheath and socket glia, and socket glia and hypodermal cells (also known as epidermal cells) at the anterior tip of the animal. In addition to its cell-autonomous function, the non-cell-autonomous function of AJM-1 in glial and hypodermal cells is required for the specification of the AWCON subtype. Furthermore, we identified a role for the DEL-1 mechanosensitive DEG/ENaC channel in the calcium signaling pathway, mediated by UNC-2 and EGL-19 voltage-activated calcium channels, that specifies AWCOFF. Together, our results suggest a mechanism in which AJM-1 promotes SLO-1 expression and antagonizes mechanosensitive calcium signaling, thereby promoting the AWCON subtype. This study provides insight into the role of mechanical force in the stochastic lateralization of olfactory neurons.

developmental biology↗

bioRxiv2026

Kinesin-1 trans-synaptically regulates synaptic localization of SARM1 for asymmetric neuron diversification

The Caenorhabditis elegans AWC olfactory neuron pair differentiates stochastically into two distinct subtypes, default AWCOFF and induced AWCON. A calcium signaling complex assembled by the TIR-1/SARM1 adaptor protein is transported from the AWC cell body to the axons, where it cell autonomously specifies the AWCOFF subtype through lateral signaling. UNC-104, the C. elegans homolog of the kinesin-3 motor protein KIF1A, acts non-cell autonomously in AWCON to control the synaptic localization of the TIR-1 signaling complex in promoting AWCOFF. Here, we identify a non-cell-autonomous role of unc-116/kinesin-1, similar to that of unc-104/kinesin-3, in promoting AWCOFF. unc-116 mutants, similar to unc-104 mutants, enhance the 2AWCON phenotype of a hypomorphic tir-1 mutant. Overexpression of unc-116 in AWC causes a 2AWCOFF phenotype, the same as the tir-1 overexpression phenotype. Like UNC-104, UNC-116 plays a non-cell-autonomous role in the AWCON cell to promote AWCOFF cell subtype by regulating the dynamic trafficking of TIR-1 along the AWC axon. UNC-116 is strikingly colocalized with UNC-104, while both are generally adjacent to TIR-1. Taken together, these results suggest a model in which UNC-116/kinesin-1 and UNC-104/kinesin-3 may work cooperatively to transport some unknown presynaptic factor(s) in the future AWCON cell that trans-synaptically regulates the dynamic trafficking of the TIR-1/SARM1 signaling complex to postsynaptic regions of the AWC axons in promoting the AWCOFF subtype.

developmental biology↗

bioRxiv2021

The kpc-1 (furin) 3'UTR promotes dendritic transport and local translation of mRNAs to regulate dendrite branching and self-avoidance of a nociceptive neuron

A recently reported Schizophrenia-associated genetic variant in the 3UTR of the human furin gene, a homolog of C. elegans kpc-1, highlights an important role of the furin 3UTR in neuronal development(1). We isolate three kpc-1 mutants that display abnormal dendrite arborization in PVD neurons and defective male mating behaviors. We show that the kpc-1 3UTR participates in dendrite branching and self-avoidance. The kpc-1 3UTR facilitates mRNA localization to branching points and contact points between sibling dendrites and promotes local protein synthesis. We identify a secondary structural motif in the kpc-1 3UTR required for dendrite self-avoidance. Animals with dma-1 receptor over-expression exhibit similar dendrite branching and self-avoidance defects that are suppressed with kpc-1 over-expression. Our results support a model in which KPC-1 proteins are synthesized at branching points and contact points to locally down-regulate DMA-1 receptors to promote dendrite branching and self-avoidance of a mechanosensory neuron important for male courtship.

neuroscience↗

bioRxiv2019

Genome-wide, integrative analysis implicates circular RNA dysregulation in autism and the corresponding circular RNA-microRNA-mRNA regulatory axes

Circular RNAs (circRNAs), a class of long non-coding RNAs, are known to be enriched in mammalian brain and neural tissues. While the effects of regulatory genetic variants on gene expression in autism spectrum disorder (ASD) have been widely reported, the role of circRNAs in ASD remains largely unknown. Here, we performed genome-wide circRNA expression profiling in post-mortem brains from individuals with ASD and controls and identified 60 circRNAs and three co-regulated modules that were perturbed in ASD. By integrating circRNA, microRNA, and mRNA dysregulation data derived from the same cortex samples, we identified 8,170 ASD-associated circRNA-microRNA-mRNA interactions. Putative targets of the axes were enriched for ASD risk genes and genes encoding inhibitory postsynaptic density (PSD) proteins, but not for genes implicated in monogenetic forms of other brain disorders or genes encoding excitatory PSD proteins. This result reflects the previous observation that ASD-derived organoids exhibit overproduction of inhibitory neurons. We further confirmed that some ASD risk genes (NLGN1, STAG1, HSD11B1, VIP, and UBA6) were indeed regulated by an upregulated circRNA (circARID1A) via sponging a downregulated microRNA (miR-204-3p) in human neuronal cells. We provided a systems-level view of landscape of circRNA regulatory networks in ASD cortex samples. We also provided multiple lines of evidence for the functional role of ASD for circRNA dysregulation and a rich set of ASD-associated circRNA candidates and the corresponding circRNA-miRNA-mRNA axes, particularly those involving ASD risk genes. Our findings thus support a role for circRNA dysregulation and the corresponding circRNA-microRNA-mRNA axes in ASD pathophysiology.

bioinformatics↗