Biology subjects

Surendran, S.

Publications and source records attributed to Surendran, S..

3 recordsLinked to original sources

bioRxiv2025

FLP-15 modulates the amplitude of body bends during locomotion in Caenorhabditis elegans

Locomotion is essential for executing most behaviours. In Caenorhabditis elegans. Efficient locomotion is exhibited as a result of the coordination of excitatory and inhibitory signals from the nervous system onto the body-wall muscles. Although neurotransmitters play a vital role in maintaining and executing coordinated movements, neuropeptides have emerged as important players in the regulation and sustenance of locomotory states. In our previous study we explored the role of the neuropeptide FLP-15 in regulating reversal frequency during foraging behaviour in C. elegans. We were also interested in exploring other possible locomotory defects in flp-15 mutant animals. In this work we show that flp-15 mutants show an increased length of reversals during foraging resulting in defects in maintaining the direction of reversals. Mutants in flp-15 exhibited a "floral" pattern of reversals as opposed to near linear patterns of reversal in wild-type control animals. We further show that the defect in maintaining the direction of reversals could be due to increased amplitude of the body-bends with flp-15 mutants showing a large increase in the mean amplitude of body-bends. Our data suggests that FLP-15 partially functions through the G-protein coupled receptor (GPCR), NPR-3, to regulates the amplitude of body-bends. Finally, we show that loss of flp-15 leads to an increase in the expression of another neuropeptide, NLP-12, whose over expression has been implicated in causing increased amplitude of body-bends allowing us to speculate that the regulation of NLP-12 by FLP-15 may allow for the observed locomotory defects in flp-15 mutant animals.

neuroscience↗

bioRxiv2025

FLP-15 functions through the GPCR NPR-3 to regulate local and global search behaviours in Caenorhabditis elegans

Foraging is essential for sustenance and well-being of all organisms. The transition from well-fed to food-deprived conditions in C. elegans triggers a localized exploration of the environment characterized by frequent reorientations. However, over time the cumulative frequency of these reorientations decreases, facilitating the transition to global search behaviour. To investigate the genetic regulation of foraging in C. elegans, we conducted a screen of neuropeptide mutants and identified several candidates involved in modulating this behaviour. Among these, neuropeptide FLP-15 emerged as a key regulator of both local and global search behaviours. Our observations revealed that FLP-15 regulates the frequency and duration of reversals during foraging. Further investigation indicated that FLP-15 is expressed in and functions through the I2 pharyngeal neuron via the G-protein coupled receptor NPR-3. Mutants lacking either flp-15 or npr-3 displayed a significant decrease in reversal frequency during local search behaviours. Interestingly, unlike wild-type animals, the reversal frequency in flp-15 and npr-3 mutants did not decrease over time. This study also describes the expression pattern of NPR-3, in a subset of head neurons, predominantly comprising of dopaminergic neurons. This expression pattern highlights a potential link between neuropeptide signalling and dopaminergic modulation of behaviour. Finally, exogenous dopamine supplementation assays revealed that FLP-15 may regulate foraging by modulating dopamine transmission, highlighting a novel neuropeptide-dopamine interaction involved in the control of foraging behaviours.

neuroscience↗

bioRxiv2024

Biochemical Impact of p300-Mediated Acetylation of Replication Protein A: Implications for DNA Metabolic Pathway Choice

Replication Protein A (RPA), a single-stranded DNA (ssDNA) binding protein, is vital for various aspects of genome maintenance such as replication, recombination, repair and cell cycle checkpoint activation. Binding of RPA to ssDNA protects it from degradation by cellular nucleases, prevents secondary structure formation and illegitimate recombination. In our current study, we identified the acetyltransferase p300 to be capable of acetylating the 70kDa subunit of RPA in vitro and within cells. The acetylation status of RPA was increased specifically during the G1/S phase of the cell cycle and also following exposure to UV-induced damage. Furthermore, we were able to specifically identify RPA directly associated with the replication fork during the S phase and UV damage to be acetylated. Based on these observations, we evaluated the impact of lysine acetylation on the biochemical properties of RPA. Investigation of binding properties of RPA revealed that acetylation of RPA increased its binding affinity to ssDNA compared to unmodified RPA. The improvement in binding efficiency was a function of DNA length with the greatest increases observed on shorter length ssDNA oligomers. Furthermore, the mechanism of acetylated RPAs increased affinity for ssDNA was shown to be a function of a slower rate of dissociation compared to the unmodified form of the RPA. Our findings demonstrate that p300-dependent, site-specific acetylation enhances RPAs DNA binding properties, potentially regulating its function during various DNA transactions.

biochemistry↗