Biology subjects

Dani, A.

Publications and source records attributed to Dani, A..

3 recordsLinked to original sources

bioRxiv2025

Cnpy1 is a candidate endoplasmic reticulum chaperone of Vomeronasal type 2 GPCRs.

Mouse vomeronasal sensory neurons are continuously generated from stem cells and differentiate to express either V1R or V2R G-protein coupled receptors (GPCRs), along with their respective Gi2 or Go G-protein subunits. We previously reported that Go-type neurons exhibit elevated expression of endoplasmic reticulum (ER) chaperones and a distinctive hypertrophic, gyroid ER architecture, suggesting specialized proteostatic demands. Here we identify a transcript for the mouse Cnpy1 gene that yields full-length Cnpy1 protein selectively expressed in and localized to the ER of Go neurons. Immunoprecipitation coupled with mass spectrometry revealed that Cnpy1 associates specifically with V2R GPCRs and multiple ER chaperones. Cnpy1 deletion resulted in mice that were deficient in Go neuronal activation upon exposure to vomeronasal stimuli and a marked reduction in male-male aggressive behavior. In the absence of Cnpy1, Go neurons develop normally till birth but undergo selective, progressive apoptosis during postnatal development. Unexpectedly, Cnpy1-null vomeronasal neurons displayed neither an obvious unfolded protein response nor defects in V2R GPCR traffic to dendritic tips, indicating that Cnpy1 is required for V2R assembly or functional maturation but dispensable for their ER export. Together, these findings identify Cnpy1 as a previously unrecognized component of an ER chaperone complex that is essential for Go neuron signaling and survival.

neuroscience↗

bioRxiv2024

Syntaxin11 Deficiency Inhibits CRAC Channel Priming To Suppress Cytotoxicity And Gene Expression In FHLH4 Patient T Lymphocytes.

Mutations in Syntaxin11, a Q-SNARE, result in a fatal immune disorder known as familial hemophagocytic lymphohistiocytosis 4 (FHLH4) in human patients. A key diagnostic feature of FHLH4 is defective T and natural killer (NK) cell cytotoxicity. Here we show that Syntaxin11 directly binds and regulates Orai1, the pore forming subunit of calcium release activated calcium (CRAC) channels. CRAC channels enable store-operated calcium entry (SOCE) from the extracellular space and are crucial for granule exocytosis and nuclear factor of activated T cell (NFAT) dependent gene expression in activated lymphocytes. Syntaxin11 depletion strongly inhibited SOCE, CRAC currents, NFAT activation, interleukin-2 gene expression and degranulation in FHLH4 patient T lymphocytes and cell lines without affecting membrane trafficking. Remarkably, defects of cytolytic granule exocytosis as well as interleukin-2 expression could be reversed by ionomycin in patient T lymphocytes and a constitutively active, H134S, mutant of Orai1 rescued calcium entry in Syntaxin11 depleted cells. Further analyses showed that Syntaxin11 primes Orai1 for optimal on-site multimeric assembly which was Stim independent but required for gating. Priming of ion channel pore subunits is, therefore, a primary function of specific SNAREs which may have preceded their role in membrane trafficking and vesicle fusion.

cell biology↗

bioRxiv2024

Single cell transcriptomics of vomeronasal neuroepithelium reveals a differential endoplasmic reticulum environment amongst neuronal subtypes

Specialized chemosensory signals elicit innate social behaviors in individuals of several vertebrate species, a process that is mediated via the accessory olfactory system (AOS). The AOS comprising the peripheral sensory vomeronasal organ has evolved elaborate molecular and cellular mechanisms to detect chemo signals. To gain insight into the cell types, developmental gene expression patterns and functional differences amongst neurons, we performed single cell transcriptomics of the mouse vomeronasal sensory epithelium. Our analysis reveals diverse cell types with gene expression patterns specific to each, which we made available as a searchable web resource accessed from www.scvnoexplorer.com. Pseudo-time developmental analysis indicates that neurons originating from common progenitors diverge in their gene expression during maturation with transient and persistent transcription factor expression at critical branch points. Comparative analysis across two of the major neuronal subtypes that express divergent GPCR families and the G-protein subunits Gnai2 or Gnao1, reveals significantly higher expression of endoplasmic reticulum (ER) associated genes within Gnao1 neurons. In addition, differences in ER content and prevalence of cubic membrane ER ultrastructure revealed by electron microscopy, indicate fundamental differences in ER function.

neuroscience↗