Biology subjects

Chander, P.

Publications and source records attributed to Chander, P..

4 recordsLinked to original sources

bioRxiv2025

The protein interactome of the Neuron Specific Gene family (NSG1-3)

The Neuron-Specific Gene (NSG) family members (NSG1-3) play critical and diverse roles in neuronal protein trafficking, but their precise molecular functions remain poorly understood. Here, we employed proximity-labeling proteomics to map the interactomes of each NSG protein. Unlabeled mass spectrometry identified over 1,000 significantly enriched interactors compared with a cytoplasmic control, revealing substantial overlap between NSG1 and NSG2, and a more divergent profile for NSG3. Gene ontology and KEGG pathway analysis confirmed established associations with glutamatergic synapses and endosomal trafficking, while also uncovering unexpected links to presynaptic machinery, inhibitory synapses, and endoplasmic reticulum-associated protein translation, particularly for NSG3. Reciprocal biotinylation patterns and co-immunoprecipitation revealed novel heteromeric complex formation between NSG1 and NSG2, with limited interactions involving NSG3. All three NSGs biotinylated core AMPA receptor subunits and auxiliary proteins, while NSG1 and NSG2 also associated with NMDA receptors, GABA receptor subunits, as well as multiple presynaptic proteins. Moreover, NSG1 and NSG2 specifically biotinylated components of multiunit tethering complexes including neuron-specific retromer, and biotinylated a preponderance of ADAM10 substrates, reinforcing their role in proteolytic processing. Finally, despite the relatively divergent interactomes of NSG1 and NSG2 compared to NSG3, all family members robustly biotinylated amyloid precursor protein (APP), suggesting possible synergistic or competitive interactions that could shape APP proteolytic processing and/or trafficking. Together, these data provide a comprehensive systems-level view of NSG protein interactions, establishing a molecular framework for future investigations into NSG-mediated neural plasticity and disease mechanisms.

neuroscience↗

bioRxiv2024

VLK drives extracellular phosphorylation of EphB2 to govern the EphB2-NMDAR interaction and injury-induced pain

Phosphorylation of hundreds of protein extracellular domains is mediated by two kinase families, yet the significance of these kinases is underexplored. Here, we find that the presynaptic release of the tyrosine directed-ectokinase, Vertebrate Lonesome Kinase (VLK/Pkdcc), is necessary and sufficient for the direct extracellular interaction between EphB2 and GluN1 at synapses, for phosphorylation of the ectodomain of EphB2, and for injury-induced pain. Pkdcc is an essential gene in the nervous system, and VLK is found in synaptic vesicles, and is released from neurons in a SNARE-dependent fashion. VLK is expressed by nociceptive sensory neurons where presynaptic sensory neuron-specific knockout renders mice impervious to post-surgical pain, without changing proprioception. VLK defines an extracellular mechanism that regulates protein-protein interaction and non-opioid-dependent pain in response to injury. One-Sentence SummarySynaptic protein-protein interactions and pain are regulated by the presynaptic release of the extracellular kinase VLK in the spinal cord.

neuroscience↗

bioRxiv2019

Transcriptomic changes due to early, chronic ethanol exposure during cortical development implicates arealization, cell-type specification, Axon Guidance and Synaptogenesis as primary determinants of Fetal Alcohol Spectrum Disorders

Fetal alcohol spectrum disorders (FASD) are described by a cluster of deficits following in utero alcohol exposure, whose effects disproportionately target the cerebral cortex. In vitro and in vivo models of FASD have successfully recapitulated multiple facets of clinical presentations, including morphological and behavioral deficits, but far less is understood regarding the molecular and genetic bases of FASD. In this study, we utilize an in vitro human pluripotent stem cell-based (hPSC) model of corticogenesis to probe the effect of early, chronic alcohol exposure on the transcriptome of developing cortical neurons. We here identify a relatively limited number of significantly altered biological pathways, including regional patterning, cell-type specification, axon guidance and synaptic function. Significant upregulation of WNT signaling-related transcripts, to the exclusion of other secreted morphogens was also observed in alcohol exposed cultures. Lastly, an overall alcohol-associated shift towards an increased caudal profile, at the expense of rostral molecular identity was observed, representing a potentially previously underappreciated FASD phenotype.

neuroscience↗

bioRxiv2019

Biodistribution and inflammatory response of intracranial delivery of scintillating nanoparticles

Nanoparticle-based delivery systems have become a popular method for targeting tumors and impermeable tissue with drugs for treatment and imaging markers for biodetection. Nanomaterials are beneficial for medical treatment because they can be modified to have increased stability and carrying capacity, and their size and surface modifications allow them to reach otherwise impenetrable tissue. Localized or systemic injection can be used for delivery of nanoparticles; however, systemic injection without appropriate surface modifications is subjected to uptake by the mononuclear phagocytic system which clears particles from the circulation rapidly limiting their accumulation at target tissue and reducing efficacy. Here we demonstrate the biodistribution of Yttrium oxyorthosilicate nanoparticles doped with Cerium after localized injection to the cerebral cortex as well as the immune response at the site of injection over time.

bioengineering↗