Biology subjects

Navakkode, S.

Publications and source records attributed to Navakkode, S..

3 recordsLinked to original sources

bioRxiv2026

Primate Hippocampus Reveals Distinct Rules for Associative Synaptic Plasticity

Long-term potentiation (LTP) is a key cellular mechanism underlying learning and memory, but its conservation across species remains unclear. Using nonhuman primates (NHPs), we examined hippocampal synaptic plasticity at Schaffer collateral- CA1 synapses. Theta-burst stimulation (TBS) reliably induced LTP in NHPs, comparable to rodents. However, unlike rodents, TBS in NHPs readily engaged synaptic tagging and capture (STC), indicating a lower threshold for associative plasticity. This was accompanied by increased expression of plasticity-related proteins, including PKM{zeta} and BDNF, suggesting enhanced recruitment of protein synthesisdependent stabilization mechanisms. These findings reveal a species-specific divergence in the molecular regulation of persistent synaptic plasticity and identify an evolutionary specialization in mechanisms supporting associative memory. Together, our results highlight limitations of rodent models in fully capturing human-relevant memory processes and underscore the importance of primate systems for translational neuroscience.

neuroscience↗

bioRxiv2020

LOCAL REGULATION AND FUNCTION OF IMPORTIN-β1 DURING TRANSCRIPTION-DEPENDENT PLASTICITY

Activity-dependent transcription is critical for the encoding of long-term memories. Regulated nuclear entry of soluble proteins is one method to relay synaptic signals to the nucleus to couple neuronal excitation with transcription. To date, the role of importin-{beta}1 in nuclear shuttling of proteins during activity-dependent transcription has always been inferred but not directly investigated. In this study, we demonstrate activity-dependent nuclear accumulation of importin-{beta}1 from the soma and the synapto-dendritic compartments. Importantly, inhibition of importin-{beta}1 mediated nuclear import during synaptic stimulation impairs long-term plasticity. We show evidence that importin-{beta}1 mRNA-ribosome complex is distributed throughout the synapto-dendritic compartment and synaptic stimulation induces importin-{beta}1 local protein synthesis. Finally, we identified candidate proteins that associate with importin-{beta}1 at the synapse and characterize NDRG1 as an importin-{beta}1 interactor that undergoes activity-dependent translocation into the nucleus. Collectively, our results highlight the crucial role of importin-{beta}1 in the nuclear import of soluble proteins during long-term plasticity.

neuroscience↗

bioRxiv2020

mTOR S-nitrosylation inhibits autophagy and lysosomal proteolysis

Mammalian Target of Rapamycin (mTOR) is a master regulator of autophagy and lysosomes, and its downstream kinase-dependent pathways have been extensively characterized. Here, we report an unexpected kinase-independent regulation of autophagy and lysosomes by S-nitrosylation at Cys423 position of mTOR that resulted in suppression of VPS34 and PIKfyve-dependent phosphoinositide synthesis. Physiologically, S-nitrosylation of mTOR reduced basal lysosomal proteolysis via nitric oxide synthase (NOS)-mediated synthesis of NO from lysosomal arginine precursor, a marker of cellular nutrition status. Significantly, we found increased lysosomal NOS-mTOR complexes in APP-PS1 Alzheimers disease (AD) murine model, and increased mTOR S-nitrosylation in AD patient-derived fibroblasts. Lastly, we demonstrated that pharmacological inhibition of NOS or overexpression of mTORCys423Ala mutant reversed lysosomal and autophagic dysfunction in AD patient-derived fibroblasts, suggesting novel therapeutic strategies for autophagosome-lysosomal activation.

cell biology↗