Biology subjects

Rogow, J. A.

Publications and source records attributed to Rogow, J. A..

4 recordsLinked to original sources

bioRxiv2026

The structural logic of insect olfactory receptor assembly and gating

Insects detect the chemical world using a large family of odorant-gated ion channels, each formed from a variable odorant-binding subunit (OR) and a single conserved co-receptor Orco. This modular organization is thought to allow tuning ORs to diversify their chemical recognition while Orco provides structural stability to the heteromer. Yet Orco can be autonomously activated by synthetic agonists, suggesting that it may contribute to channel gating rather than serving solely as a structural scaffold. Here, we combine cryo-electron microscopy with analyses of receptor stoichiometry and function to define the structural logic underlying Orco-OR assembly and gating. We show that Orco retains the canonical ligand-binding pocket of ORs but is chemically insulated from environmental odorants by a phospholipid that occupies this site. The Orco agonist VUAA4 instead binds a membrane-accessible crevice adjacent to the gate, defining a distinct site of allosteric modulation. We further demonstrate that Orco-OR heteromers can assemble in multiple stoichiometries through shape complementarity within the intracellular anchor domain and resolve structures with both a 3:1 and 2:2 architecture. Receptors constrained to a 2:2 stoichiometry are functional but productive gating requires cooperative engagement of multiple subunits within the heteromer. Comparison with the distinct gating states of a basal homomeric olfactory receptor suggests that existing Orco-OR structures capture nonconductive intermediates within the broader conformational landscape of this receptor family. Together, these findings suggest how Orco can flexibly assemble and function with highly divergent ORs, acting not simply as a structural scaffold but as an integral partner in cooperative channel gating, thereby enabling the extraordinary diversification of insect olfactory receptors.

neuroscience↗

bioRxiv2026

An integrated RNA-centric imaging and omics approach reveals distinct properties and composition of neuronal RNA granules

RNA granules are essential regulators of post-transcriptional gene expression, enabling mRNA transport, localization, and local translation in neurons. The localized transcriptome is diverse; however, how different mRNAs are organized into granules for efficient localization and translation remains unknown. Here, we combine real-time endogenous single RNA imaging with protein and RNA proximity labeling to investigate two distinct endogenous neuronal mRNA granule populations, Actb and Arc, in stimulated primary hippocampal neurons. Using orthogonal RNA labeling systems in a dual knock-in mouse model, we show that Actb and Arc mRNAs are packaged into spatially segregated granules with distinct trafficking dynamics, localization kinetics, and responses to synaptic stimulation. Actb granules displayed rapid and sustained localization, whereas Arc granules showed delayed, transient recruitment, consistent with their respective roles in structural and activity-dependent plasticity. Proximity labeling reveals that these granules are distinct in their mRNA composition, despite sharing core RNA-binding proteins, suggesting that shared cis-regulatory elements within mRNA 3UTR regions drive selective co-packaging of mRNAs into unique granules. Together, these findings demonstrate that neuronal mRNAs are differentially sorted into molecularly and functionally distinct granules, providing a framework for understanding how precise spatio-temporal control of mRNA localization and translation is achieved across complex neuronal arbors.

neuroscience↗

bioRxiv2026

Modular presynaptic assemblages scale to postsynaptic partner number

Behavioral diversification can arise through, and is constrained by, evolutionary and inter-individual differences in neural circuit development. Moreover, alteration of focal neural parameters changes the environment in which cells connect into circuits. In the mushroom body, an associative learning center of arthropods, the number of principal Kenyon cells varies widely across species and among individuals. How such variation is developmentally accommodated by projection neurons, which provide sensory input to Kenyon cells, is not understood. In Drosophila melanogaster, we previously demonstrated that projection neurons scale their presynaptic bouton number to Kenyon cell population size. Here, we identify the developmental mechanisms underlying this input flexibility. Boutons arise from projection neuron axonal collaterals; we find that a PNs collateral number is subtype-specific and serves as the substrate through which bouton number scales to Kenyon cell population size. Independent of projection neuron identity or Kenyon cell number, individual collaterals most often produce just one bouton, suggesting collaterals are modular cell biological bouton units. Developing projection neurons initially overproduce nascent collaterals in the early pupa. The set of nascent collaterals that mature and eventually bear boutons is conditional on Kenyon cell number, thereby executing scaling. Finally, early boutons bear filopodia that frequently contact neighboring PN processes, suggesting that bouton-bouton interactions contribute to shaping these structures.

neuroscience↗

bioRxiv2019

Presynaptic developmental plasticity allows robust sparse wiring of the Drosophila mushroom body

In order to represent complex stimuli, principle neurons of associative learning regions receive combinatorial sensory inputs. Density of combinatorial innervation is theorized to determine the number of distinct stimuli that can be represented and distinguished from one another, with sparse innervation thought to optimize the complexity of representations in networks of limited size. How the convergence of combinatorial inputs to principle neurons of associative brain regions is established during development is unknown. Here, we explore the developmental patterning of sparse olfactory inputs to Kenyon cells of the Drosophila melanogaster mushroom body. By manipulating the ratio between pre- and post-synaptic cells, we find that postsynaptic Kenyon cells set convergence ratio: Kenyon cells produce fixed distributions of dendritic claws while presynaptic processes are plastic. Moreover, we show that sparse odor responses are preserved in mushroom bodies with reduced cellular repertoires, suggesting that developmental specification of convergence ratio allows functional robustness.

neuroscience↗