Biology subjects

Sigrist, S.

Publications and source records attributed to Sigrist, S..

3 recordsLinked to original sources

bioRxiv2025

Presynaptic Release Probability Determines the Need for Sleep

Sleep is universal among animals with synapses, yet the synaptic functions determining the need for sleep remain elusive. By directly measuring synaptic transmission at anatomically defined synapses in Drosophila, we found that synaptic strength remained stable or declined after sleep deprivation in a circuit-specific manner. In contrast, presynaptic release probability (Pr) consistently decreased with sleep loss across circuits and species, stemming from reduced Ca2+ influx or weakened vesicle-channel coupling at presynaptic terminals, and recovered after sleep. Bidirectional manipulations of Pr altered sleep pressure, establishing a causal relationship between presynaptic function and sleep need. Non-synaptic sleep-regulatory signaling pathways consistently modulate Pr but not synaptic strength. Thus, our findings identify Pr, rather than synaptic strength, as the conserved synaptic substrate underlying sleep need.

neuroscience↗

bioRxiv2021

Translational control of polyamine metabolism by CNBP is required for Drosophila locomotor function

Microsatellite expansions of CCTG repeats in the CNBP gene leads to accumulation of toxic RNA and have been associated to DM2. However, it is still unclear whether the dystrophic phenotype is also linked to CNBP decrease, a conserved CCHC-type zinc finger RNA binding protein that regulates translation and is required for mammalian development. Here we show that depletion of Drosophila CNBP in muscles causes age-dependent locomotor defects that are correlated with impaired polyamine metabolism. We demonstrate that the levels of ornithine decarboxylase (ODC) and polyamines are significantly reduced upon dCNBP depletion. Of note, we show a reduction of the CNBP-polyamine axis in muscle from DM2 patients. Mechanistically, we provide evidence that dCNBP controls polyamine metabolism through binding dOdc mRNA and regulating its translation. Remarkably, the locomotor defect of dCNBP-deficient flies is rescued by either polyamine supplementation or dOdc1 overexpression. We suggest that this dCNBP function is evolutionarily conserved in vertebrates with relevant implications for CNBP-related pathophysiological conditions. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=195 SRC="FIGDIR/small/441910v2_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@a8c31corg.highwire.dtl.DTLVardef@1a18260org.highwire.dtl.DTLVardef@76a3d4org.highwire.dtl.DTLVardef@fdd041_HPS_FORMAT_FIGEXP M_FIG C_FIG CNBP controls muscle function by regulating the polyamine metabolism O_LILack of dCNBP impairs locomotor function through ODC-polyamine downregulation C_LIO_LIdCNBP binds dOdc mRNA and regulates its translation C_LIO_LIPolyamine supplementation or dOdc1 reconstitution rescues locomotor defects C_LIO_LICNBP-ODC-polyamine levels are reduced in muscle of DM2 patients C_LI

genetics↗

bioRxiv2019

Maintenance of cell type-specific connectivity and circuit function requires Tao kinase

Sensory circuits are typically established during early development, yet how circuit specificity and function are maintained during organismal growth has not been elucidated. To gain insight we quantitatively investigated synaptic growth and connectivity in the Drosophila nociceptive network during larval development. We show that connectivity between primary nociceptors and their downstream neurons scales with animal size. We further identified the conserved Ste20-like kinase Tao as a negative regulator of synaptic growth required for maintenance of circuit specificity and connectivity. Loss of Tao kinase resulted in exuberant postsynaptic specializations and aberrant connectivity during larval growth. Using functional imaging and behavioral analysis we show that loss of Tao-induced ectopic synapses with inappropriate partner neurons are functional and alter behavioral responses in a connection-specific manner. Our data show that fine-tuning of synaptic growth by Tao kinase is required for maintaining specificity and behavioral output of the neuronal network during animal growth.

neuroscience↗