Biology subjects

Yanez, A.

Publications and source records attributed to Yanez, A..

6 recordsLinked to original sources

bioRxiv2026

GluDs are ionotropic dopamine receptors tuned by G-proteins

Dopamine is a neurotransmitter essential for cognition, and its dysregulation is associated with neurological diseases1,2. Historically, dopamine has been understood to signal exclusively through metabotropic receptors3. Delta-type ionotropic glutamate receptors (GluDs), which have recently been established as ligand-gated ion channels4,5, are fundamental for synaptic maintenance, are implicated in neurological disorders, and co-localize with dopaminergic machinery. Here, we report that dopamine is a direct agonist of GluDs, eliciting ionotropic activity, as visualized by cryo-electron microscopy (cryo-EM), bilayer recordings, mutagenesis, and patch clamp recordings. Dopamine binds to the GluD ligand binding domain, inducing clamshell closure and channel activation through a distinct molecular interface. GluD channel activity is tightly regulated by G-proteins, which act as molecular switches to tune GluD activity: free G{beta}{gamma} inhibits ligand-gating, while G or inactive G-protein heterotrimers enable dopamine-induced GluD currents. This tuning of GluD activity by G-proteins is uncoupled in a point mutation associated with neurodegeneration. These findings expand mechanisms of neuronal dopaminergic signaling, uncover how G-proteins tune GluD channel activity, and provide a framework for targeting GluDs in neurological diseases.

biophysics↗

bioRxiv2026

SlCIPK26 enhances tomato fertility by activating the K+ transporter SlHAK5 in reproductive tissues

In tomato plants, the potassium (K) transporter SlHAK5 is integral to root K uptake and overall plant fertility. Under K deficiency, SlHAK5 expression is induced in roots and the encoded transporter is activated via the Ca{superscript 2}-sensing CIPK/CBL complex SlCIPK23/SlCBL1-9. In Arabidopsis, multiple CIPK/CBL complexes can activate AtHAK5, providing alternative regulatory pathways that enhance K uptake. However, the architecture of CIPK/CBL signaling networks has diverged among plant species, necessitating species-specific identification of novel regulatory components. Accordingly, we screened additional tomato CIPK proteins for their capacity to modulate SlHAK5 activity in yeast. SlCIPK15 and SlCIPK26 emerged as potent activators of SlHAK5, acting in concert with SlCBL9. Functional characterization of slcipk15 and slcipk26 mutants revealed that neither contributed significantly to SlHAK5-mediated K uptake in roots. Conversely, both mutants exhibited impaired pollen tube elongation, correlating with reduced K content in pollen relative to wild type. Notably, slcipk26 mutants displayed more severe pollen defects, phenocopying the slhak5 mutant. Further analyses demonstrated that slcipk26 plants suffered compromised seed set and pistil function, paralleling the reproductive deficiencies observed in slhak5 mutants. These findings implicate SlCIPK26 as the principal regulator of SlHAK5 in reproductive tissues. Collectively, our data underscore the role of CIPK paralogs in orchestrating tissue-specific regulation of target proteins, thereby enabling fine-tuned modulation of K transport essential for both vegetative and reproductive development.

plant biology↗

bioRxiv2026

Testing fundamental hypotheses of colonization success in the ferns

Background and AimsNon-native species are now ubiquitous members of regional floras. The factors that lead to establishment and dominance of non-native species are continuously debated. Fundamental hypotheses about drivers of invasion success include the role of phylogeny, polyploidy, genome size, and rapid niche evolution. These hypotheses have been tested in the seed plants, but ferns, the second largest group of vascular plants, have rarely been considered in these analyses, despite making up a non-trivial portion of non-native floras. MethodsWe compiled a dataset of global non-native ferns and categorized them along the invasion spectrum using descriptions from the literature and natural history collections. Using this dataset, we assessed I) the taxonomic diversity and phylogenetic clustering of non-native ferns, II) the geographic distribution of fern introductions, testing for shifts in climatic niches, and III) test for the association of invader traits across the invasion continuum, including smaller genome sizes and higher ploidal levels. Key ResultsWe generated a dataset that includes 83 taxa; of these, we classified 18 as casual, 35 as naturalized (but not invasive), and 30 as invasive. Using this dataset, we found I) weak or no phylogenetic clustering of non-native ferns, II) some regions are overrepresented as sources and recipients of introductions, III) climatic niches are often conserved between native and introduced ranges, but can differ between introductions, IV) naturalized ferns have smaller genomes, and V) invaders have higher ploidal levels. ConclusionsWe integrated regional floras, occurrence and climate data, phylogeny, and cytology to test fundamental hypotheses regarding the colonization success of ferns. This study provides insights into the ecological, genomic, and phylogenetic features associated with the colonization of new habitats by non-native ferns, a largely overlooked portion of non-native plant taxa.

evolutionary biology↗

bioRxiv2025

Excitatory nicotinic signaling drives action potential bursting in dopaminergic axons

Nicotinic acetylcholine receptors (nAChRs) facilitate striatal dopamine transmission but also suppress dopamine release during high-frequency stimulation, suggesting they act as as low pass filters of dopamine release. Because axonal excitability is key a determinant of transmission, we combined axonal recordings and calcium imaging to define the physiological conditions under which nAChRs bidirectionally control dopaminergic axons. Activation of cholinergic interneuron (CINs) recruited nAChRs to enhance dopaminergic axon signals under moderate activation but suppressed signals after strong high-frequency stimulation. Axonal recordings revealed that single-pulse striatal stimulation triggered a rapid ([~]125 Hz) burst of 2-3 nAChR-driven spikes in dopaminergic axons followed by a brief refractory period that inhibited further axon spiking. In sum, we show that nAChRs mainly enhance local excitability of striatal dopaminergic axons but also trigger axonal bursting that suppresses axonal excitability. This mechanism expands the computational power of dopaminergic axons and explains the apparent nAChR-mediated low-pass filtering of dopamine release.

neuroscience↗

bioRxiv2025

Overexpression of alpha synuclein in Midbrain Dopamine Neurons Reduces Dopamine Release Without Cell Loss and Drives Mild Motor Deficits in Mice

It has proven challenging to faithfully recapitulate the key pathological, physiological, and behavioral features of Parkinsons Disease (PD) in animals. Here we used adeno-associated virus (AAV) vectors to achieve cell type-specific overexpression of wild-type human -synuclein (syn) and a fluorophore (mCherry) in midbrain dopamine neurons to model PD in mice. We found that AAVs drove selective expression of both syn and mCherry in midbrain dopamine neurons. In conjunction with approximately 2-fold overexpression of syn, we found several histopathological markers of PD-like pathology, including progressive accumulation of phosphorylated and aggregated syn, ubiquitin, and a reduction in the expression of tyrosine hydroxylase, without overt cell loss. In parallel, syn overexpression drove a profound loss of evoked dopamine release, without a substantive change in the intrinsic properties of dopamine neurons, nor in striatal dopamine content. Finally, syn overexpression led to mild locomotor deficits. Together, these findings suggest that moderate syn overexpression can mimic some aspects of premotor and early symptomatic phases of PD, including markers of Lewy Body-like pathology and functional loss of evoked dopamine release. This model may be useful for investigating cellular and circuit mechanisms related to PD pathogenesis and progression.

neuroscience↗

bioRxiv2024

Presynaptic GABAA receptors control integration of nicotinic input onto dopaminergic axons in the striatum

Axons of dopaminergic neurons express gamma-aminobutyric acid type-A receptors (GABAARs) and nicotinic acetylcholine receptors (nAChRs) which are both independently positioned to shape striatal dopamine release. Using electrophysiology and calcium imaging, we investigated how interactions between GABAARs and nAChRs influence dopaminergic axon excitability. Direct axonal recordings showed that benzodiazepine application suppresses subthreshold axonal input from cholinergic interneurons (CINs). In imaging experiments, we used the first temporal derivative of presynaptic calcium signals to distinguish between direct- and nAChR-evoked activity in dopaminergic axons. We found that GABAAR antagonism with gabazine selectively enhanced nAChR-evoked axonal signals. Acetylcholine release was unchanged in gabazine suggesting that GABAARs located on dopaminergic axons, but not CINs, mediated this enhancement. Unexpectedly, we found that a widely used GABAAR antagonist, picrotoxin, inhibits axonal nAChRs and should be used cautiously for striatal circuit analysis. Overall, we demonstrate that GABAARs on dopaminergic axons regulate integration of nicotinic input to shape presynaptic excitability.

neuroscience↗