
드로소필라에서 냄새 자체가 미각 수용체 신경세포를 활성화하여 섭식 반사를 유발한다.


coremsg

Odors are intimately tied to the taste system to aid food selection and determine the sensory experience of food. However, how smell and taste are integrated in the nervous system to drive feeding behavior remains largely unknown. We show in Drosophila that odors alone activate gustatory receptor neurons (GRNs) and trigger proboscis extension reflex (PER), a canonical taste-evoked feeding behavior. Odor-evoked PER requires the function of sugar-sensing GRNs but not the olfactory organs. Calcium imaging shows that GRNs directly respond to odors. Odor-evoked PER is mediated by the Gr5a receptor, and is bidirectionally modulated by specific olfactory binding proteins. Finally, odors and sucrose co-applied to GRNs synergistically enhance PER. These results reveal a cell-intrinsic mechanism for odor-taste multimodal integration that takes place as early as in GRNs, indicating that unified chemosensory experience is a product of layered integration in peripheral neurons and in the brain.

### Competing Interest Statement

The authors have declared no competing interest.

Odors drive feeding through gustatory receptor neurons in Drosophila

냄새가-드로소필라의-미각-수용체-신경세포를-통해-섭식을-유도한다


냄새가 드로소필라의 미각 수용체 신경세포를 통해 섭식을 유도한다


title_rewrite


Fasciclin 3 isoform G의 과발현은 후각 수용체 신경세포에서 caspase의 비치사성 활성화를 촉진한다.


The nervous system undergoes functional modification independent on cell turn over. Caspase participates in reversible neuronal modulation via non-lethal activation. However, the mechanism that enables non-lethal activation remains unclear. Here, we analyzed proximal proteins of Drosophila executioner caspase in the adult brain using TurboID. We discovered that executioner caspase Drice is, as an inactive proform, proximal to cell membrane proteins, including a specific splicing isoform of cell adhesion molecule Fasciclin 3 (Fas3), Fas3G. To investigate whether sequestration of executioner caspase to plasma membrane of axons is the mechanism for non-lethal activation, we developed a Gal4-Manipulated Area-Specific CaspaseTracker/CasExpress system for sensitive monitoring of caspase activity near plasma membrane. We demonstrated that Fas3G -overexpression promotes caspase activation in olfactory receptor neurons without killing them, by inducing expression of initiator caspase Dronc, which also comes close to Fas3G. Physiologically, Fas3G -overexpression facilitated non-lethal activation suppresses innate olfactory attraction behavior. Our findings suggest that subcellularly-restricted caspase activation, defined by caspase proximal proteins, is the mechanism for non-lethal activation, opening the methodological development of reversible modification of neuronal function via regulating caspase proximal proteins.

### Competing Interest Statement

The authors have declared no competing interest.

Executioner caspase is proximal to Fasciclin 3 which facilitates non-lethal activation in Drosophila olfactory receptor neurons

실행기-caspase가-fasciclin-3와-근접하여-drosophila-후각-수용체-신경세포에서-비치사성-활성화를-촉진한다


실행기 caspase가 Fasciclin 3와 근접하여 Drosophila 후각 수용체 신경세포에서 비치사성 활성화를 촉진한다



녹내장 관련 옵티뉴린 돌연변이는 시신경 축삭 내에서 정지된 미토콘드리아와 미토파지 기구의 증가를 유발하며, 이는 축삭 외부로 방출된 미토콘드리아의 성상세포에 의한 분해로 이어진다.


We previously described a process referred to as transmitophagy where mitochondria shed by retinal ganglion cell (RGC) axons are transferred to and degraded by surrounding astrocytes in the optic nerve head of mice. Since the mitophagy receptor Optineurin (OPTN) is one of few large- effect glaucoma genes and axonal damage occurs at the optic nerve head in glaucoma, here we explored whether OPTN mutations perturb transmitophagy. Live-imaging of Xenopus laevis optic nerves revealed that diverse human mutant but not wildtype OPTN increase stationary mitochondria and mitophagy machinery and their colocalization within, and in the case of the glaucoma-associated OPTN mutations also outside of, RGC axons. These extra-axonal mitochondria are degraded by astrocytes. Our studies support the view that in RGC axons under baseline conditions there are low levels of mitophagy, but that glaucoma-associated perturbations in OPTN result in increased axonal mitophagy involving the shedding and astrocytic degradation of the mitochondria.

![Figure][1]</img>

### Competing Interest Statement

The authors have declared no competing interest.

 [1]: pending:yes

Glaucoma-associated Optineurin mutations increase transmitophagy in a vertebrate optic nerve

녹내장-관련-옵티뉴린-돌연변이는-척추동물-시신경에서-전달미토파지를-증가시킨다


녹내장 관련 옵티뉴린 돌연변이는 척추동물 시신경에서 전달미토파지를 증가시킨다



iPSC 유래 피질 신경세포의 축삭과 세포체 간 전사체 프로파일이 뚜렷하게 구분되며, KIF1C 결손이 축삭 전사체에 광범위한 변화를 유발함


Neuronal function and pathology are deeply influenced by the distinct molecular profiles of the axon and soma. Traditional studies have often overlooked these differences due to the technical challenges of compartment specific analysis. In this study, we employ a robust RNA-sequencing (RNA-seq) approach, using microfluidic devices, to generate high-quality axonal transcriptomes from iPSC-derived cortical neurons (CNs). We achieve high specificity of axonal fractions, ensuring sample purity without contamination. Comparative analysis revealed a unique and specific transcriptional landscape in axonal compartments, characterized by diverse transcript types, including protein-coding mRNAs, ribosomal proteins (RPs), mitochondrial-encoded RNAs, and long non-coding RNAs (lncRNAs). Previous works have reported the existence of transcription factors (TFs) in the axon. Here, we detect a subset of previously unreported TFs specific to the axon and indicative of their active participation in transcriptional regulation. To investigate transcripts and pathways essential for central motor neuron (MN) degeneration and maintenance we analyzed KIF1C-knockout (KO) CNs, modeling hereditary spastic paraplegia (HSP), a disorder associated with prominent length-dependent degeneration of central MN axons. We found that several key factors crucial for survival and health were absent in KIF1C-KO axons, highlighting a possible role of these also in other neurodegenerative diseases. Taken together, this study underscores the utility of microfluidic devices in studying compartment-specific transcriptomics in human neuronal models and reveals complex molecular dynamics of axonal biology. The impact of KIF1C on the axonal transcriptome not only deepens our understanding of MN diseases but also presents a promising avenue for exploration of compartment specific disease mechanisms.

### Competing Interest Statement

The authors have declared no competing interest.

*   ALS
    :   Amyotrophic lateral sclerosis
    APC
    :   Adenomatous-polyposis-coli-protein
    BDNF
    :   Brain derived neurotrophic factor
    bp
    :   basepairs
    BP
    :   Biological process
    CC
    :   Cellular component
    CMT
    :   Charcot-Marie-Tooth
    CN
    :   Cortical neuron
    CNS
    :   Central nervous system
    DAI
    :   Day after induction
    DRG
    :   Dorsal root ganglia
    EJC
    :   Exon junction complex
    GDNF
    :   Glial cell line-derived neurotrophic factor
    GO
    :   Gene ontology
    GWAS
    :   Genome-wide association studies
    HSP
    :   Hereditary spastic paraplegia
    HD
    :   Huntington disease
    IPSC
    :   Induced pluripotent stem cell
    KIF1C
    :   Kinesin family member 1 C
    KO
    :   knockout
    MF
    :   Molecular function
    MN
    :   Motor neuron
    mt
    :   Mitochondrial
    NGF
    :   Nerve growth factor
    QC
    :   Quality control
    PC
    :   Principal component
    PCA
    :   Principal component analysis
    RP
    :   Ribosomal protein
    SMA
    :   Spinal muscular atrophy
    SPG58
    :   Hereditary spastic paraplegia type 58
    STMN
    :   Stathmin
    TF
    :   Transcription Factor
    TPM
    :   Transcripts per million
    RNA-seq
    :   RNA-sequencing
    WT
    :   Wild-type

Unraveling Axonal Transcriptional Landscapes: Insights from iPSC-Derived Cortical Neurons and Implications for Motor Neuron Degeneration

ipsc-유래-피질-신경세포의-축삭-전사체-분석을-통한-운동신경세포-퇴행의-통찰


iPSC 유래 피질 신경세포의 축삭 전사체 분석을 통한 운동신경세포 퇴행의 통찰



비만은 허기 신경세포 주변의 분자 그물 축적으로 인한 인슐린 신호 전달 장애가 주요 원인이다.


Neuronal insulin resistance caused by excess extracellular matrix.

Obesity is driven by a build-up of molecular mesh around hunger neurons

비만은-허기-신경세포-주변의-분자-그물-축적으로-인해-발생한다


비만은 허기 신경세포 주변의 분자 그물 축적으로 인해 발생한다



초기 생활 경험이 드로솔파키닌 신호전달을 통해 성인기 사회적 행동의 가소성을 인코딩한다.


Drosophila establishes social clusters in groups, yet the underlying principles remain poorly understood. Here we performed a systemic analysis of social network behavior (SNB) that quantifies individual social distance (SD) in a group over time. The SNB assessment in 175 inbred strains from the Drosophila Genetics Reference Panel revealed a tight association of short SD with long developmental time, low food intake, and hypoactivity. The developmental inferiority in short-SD individuals was compensated by their group culturing. By contrast, developmental isolation silenced the beneficial effects of social interactions in adults and blunted the plasticity of SNB under physiological challenges. Transcriptome analyses showed genetic diversity for SD traits, whereas social isolation reprogrammed select genetic pathways, regardless of SD phenotypes. In particular, social deprivation suppressed the expression of the neuropeptide Drosulfakinin ( Dsk ) in three pairs of adult brain neurons. Male-specific DSK signaling to Cholecystokinin-like receptor 17D1 mediated the SNB plasticity. In fact, transgenic manipulations of the DSK signaling were sufficient to imitate the state of social experience. Given the functional conservation of mammalian Dsk homologs, we propose that animals have evolved a dedicated neural mechanism to encode early-life experience and transform group properties adaptively.

### Competing Interest Statement

The authors have declared no competing interest.

Drosulfakinin signaling encodes early-life memory for adaptive social plasticity

자연-집단에서-드로설파키닌-신호전달이-적응적-사회적-가소성을-위한-초기-경험-기억을-인코딩한다


자연 집단에서 드로설파키닌 신호전달이 적응적 사회적 가소성을 위한 초기 경험 기억을 인코딩한다



msiCAT-tailing은 ATP5α 단백질의 기능을 변화시켜 미토콘드리아 막전위를 증가시키고 MPTP 개방을 억제함으로써 신경교종 세포의 생존, 이동 및 약물 저항성을 높인다.


The rapid and sustained proliferation in cancer cells requires accelerated protein synthesis. Accelerated protein synthesis and disordered cell metabolism in cancer cells greatly increase the risk of translation errors. ribosome-associated quality control (RQC) is a recently discovered mechanism for resolving ribosome collisions caused by frequent translation stalls. The role of the RQC pathway in cancer initiation and progression remains controversial and confusing. In this study, we investigated the pathogenic role of mitochondrial stress-induced protein carboxyl-terminal terminal alanine and threonine tailing (msiCAT-tailing) in glioblastoma (GBM), which is a specific RQC response to translational arrest on the outer mitochondrial membrane. We found that msiCAT-tailed mitochondrial proteins frequently exist in glioblastoma stem cells (GSCs). Ectopically expressed msiCAT-tailed mitochondrial ATP synthase F1 subunit alpha (ATP5α) protein increases the mitochondrial membrane potential and blocks mitochondrial permeability transition pore (MPTP) formation/opening. These changes in mitochondrial properties confer resistance to staurosporine (STS)-induced apoptosis in GBM cells. Therefore, msiCAT-tailing can promote cell survival and migration, while genetic and pharmacological inhibition of msiCAT-tailing can prevent the overgrowth of GBM cells.

Highlights 

### Competing Interest Statement

The authors have declared no competing interest.

The mitochondrial stress-induced protein carboxyl-terminal alanine and threonine tailing (msiCAT-tailing) promotes glioblastoma tumorigenesis by modulating mitochondrial functions

신경교종-발생에-기여하는-미토콘드리아-스트레스-유도-단백질-카복실-말단-알라닌-및-트레오닌-부가-msicat-tailing-기전


신경교종 발생에 기여하는 미토콘드리아 스트레스 유도 단백질 카복실 말단 알라닌 및 트레오닌 부가(msiCAT-tailing) 기전



Ciona 미충체는 접착 기간과 강도를 측정하여 적절한 시기에 변태를 개시하는데, 이를 위해 자극성 및 억제성 G-단백질 신호 전달 경로가 상호 작용하여 cAMP 축적을 조절한다.


Larvae of the ascidian Ciona initiate metamorphosis tens of minutes after adhesion to a substratum via its adhesive organ. The gap between adhesion and metamorphosis initiation is suggested to ensure the rigidity of adhesion, allowing Ciona to maintain settlement after losing locomotive activity through metamorphosis. The mechanism producing the gap is unknown. Here, by combining gene functional analyses, pharmacological analyses, and live imaging, we propose that the gap represents the time required for sufficient cAMP accumulation to trigger metamorphosis. Not only the Gs pathway but also the Gi and Gq pathways are involved in the initiation of metamorphosis in the downstream signaling cascade of the neurotransmitter GABA, the known initiator of Ciona metamorphosis. The mutual crosstalk of stimulatory and inhibitory G-proteins functions as the accelerator and brake for cAMP production, ensuring the faithful initiation of metamorphosis at an appropriate time and in the right situation.

### Competing Interest Statement

The authors have declared no competing interest.

Stimulatory and inhibitory G-protein signaling relays drive cAMP accumulation for timely metamorphosis in the chordate Ciona

접착-기간과-강도를-측정하여-적절한-시기에-변태를-개시하는-미충체-ciona의-신호-전달-기작


접착 기간과 강도를 측정하여 적절한 시기에 변태를 개시하는 미충체 Ciona의 신호 전달 기작



도파민은 해마 신경세포에서 단백질 합성을 증가시키며, 이를 통해 도파민 의존성 장기 강화(DA-LTP)를 가능하게 한다.


The reward and novelty related neuromodulator dopamine plays an important role in hippocampal long-term memory, which is thought to involve protein synthesis-dependent synaptic plasticity. However, the direct effects of dopamine on protein synthesis, and the functional implications of newly synthesized proteins for synaptic plasticity, have not yet been investigated. We have previously reported that timing-dependent synaptic depression (t-LTD) can be converted into potentiation by dopamine application during synaptic stimulation (Brzsoko et al., 2015) or postsynaptic burst activation ([Fuchsberger et al., 2022][1]). Here we show that dopamine increases protein synthesis in mouse hippocampal CA1 neurons, enabling dopamine-dependent long-term potentiation (DA-LTP). We found that neuronal activity is required for the dopamine-induced increase in protein synthesis, which is mediated via the Ca2+-sensitive adenylate cyclase (AC) subtypes 1/8, cAMP, and cAMP-dependent protein kinase (PKA). Furthermore, dopamine induced a protein synthesis-dependent increase in the AMPA receptor subunit GluA1, but not GluA2. We found that DA-LTP is absent in GluA1 knock-out mice and that it requires calcium-permeable AMPA receptors. Taken together, our results suggest that dopamine together with neuronal activity controls synthesis of plasticity-related proteins, including GluA1, which enable DA-LTP via a signalling pathway distinct from that of conventional LTP.

### Competing Interest Statement

The authors have declared no competing interest.

 [1]: #ref-16

Dopamine increases protein synthesis in hippocampal neurons enabling dopamine-dependent LTP

도파민이-해마-신경세포에서-단백질-합성을-증가시켜-도파민-의존성-ltp를-가능하게-한다


도파민이 해마 신경세포에서 단백질 합성을 증가시켜 도파민 의존성 LTP를 가능하게 한다



TIMM50 결핍은 대부분의 미토콘드리아 단백질 수준에는 영향을 미치지 않지만, 산화적 인산화 및 미토콘드리아 리보솜 복합체의 감소를 초래하여 ATP 생산 저하, 신경 세포 내 미토콘드리아 이동 장애, 그리고 신경 활성 증가 등의 결과를 초래한다.


TIMM50, an essential TIM23 complex subunit, is suggested to facilitate the import of ∼60% of the mitochondrial proteome. In this study, we characterized a TIMM50 disease causing mutation in human fibroblasts, and noted significant decreases in TIM23 core protein levels (TIMM50, TIMM17A/B, and TIMM23). Strikingly, TIMM50 deficiency had no impact on the steady state levels of most of its substrates, challenging the currently accepted import dogma of the essential general import role of TIM23 and suggesting that fully functioning TIM23 complex is not essential for maintaining the steady state level of the majority of mitochondrial proteins. As TIMM50 mutations have been linked to severe neurological phenotypes, we aimed to characterize TIMM50 defects in manipulated mammalian neurons. TIMM50 knockdown in mouse neurons had a minor effect on the steady state level of most of the mitochondrial proteome, supporting the results observed in patient fibroblasts. Amongst the few affected TIM23 substrates, a decrease in the steady state level of components of the intricate oxidative phosphorylation and mitochondrial ribosome complexes was evident. This led to declined respiration rates in fibroblasts and neurons, reduced cellular ATP levels and defective mitochondrial trafficking in neuronal processes, possibly contributing to the developmental defects observed in patients with TIMM50 disease. Finally, increased electrical activity was observed in TIMM50 deficient mice neuronal cells, which correlated with reduced levels of KCNJ10 and KCNA2 plasma membrane potassium channels, likely underlying the patients’ epileptic phenotype.

### Competing Interest Statement

The authors have declared no competing interest.

Biochemical and neurophysiological effects of deficiency of the mitochondrial import protein TIMM50

timm50-결핍이-초래하는-생화학적-및-신경생리학적-영향


TIMM50 결핍이 초래하는 생화학적 및 신경생리학적 영향
