Biology subjects

Smolin, N.

Publications and source records attributed to Smolin, N..

3 recordsLinked to original sources

bioRxiv2024

Neuronal identity control at the resolution of a single transcription factor isoform

The brain exhibits remarkable neuronal diversity which is critical for its functional integrity. From the sheer number of cell types emerging from extensive transcriptional, morphological, and connectome datasets, the question arises of how the brain is capable of generating so many unique identities. Terminal selectors are transcription factors hypothesized to determine the final identity characteristics in post-mitotic cells. Which transcription factors function as terminal selectors and the level of control they exert over different terminal characteristics are not well defined. Here, we establish a novel role for the transcription factor broad as a terminal selector in Drosophila melanogaster. We capitalize on existing large sequencing and connectomics datasets and employ a comprehensive characterization of terminal characteristics including Perturb-seq and whole-cell electrophysiology. We find a single isoform broad-z4 serves as the switch between the identity of two visual projection neurons LPLC1 and LPLC2. Broad-z4 is natively expressed in LPLC1, and is capable of transforming the transcriptome, morphology, and functional connectivity of LPLC2 cells into LPLC1 cells when perturbed. Our comprehensive work establishes a single isoform as the smallest unit underlying an identity switch, which may serve as a conserved strategy replicated across developmental programs.

neuroscience↗

bioRxiv2022

Visual projection neuron convergence and compensation in developing sensorimotor circuits in the Drosophila optic glomeruli

Behaviorally relevant, higher order representations of an animals environment are built from the convergence of visual features encoded in the early stages of visual processing. Although developmental mechanisms that generate feature encoding channels in early visual circuits have been uncovered, relatively little is known about the mechanisms that direct feature convergence to enable appropriate integration into downstream circuits. Here we explore the development of a collision detection sensorimotor circuit in Drosophila melanogaster, the convergence of visual projection neurons (VPNs) onto the dendrites of a large descending neuron, the giant fiber (GF). We find VPNs encoding different visual features establish their respective territories on GF dendrites through sequential axon arrival during development. Physical occupancy, but not developmental activity, is important to maintain territories. Ablation of one VPN results in the expansion of remaining VPN territories and functional compensation that enables the GF to retain responses to ethologically relevant visual stimuli. GF developmental activity, observed using a pupal electrophysiology preparation, appears after VPN territories are established, and likely contributes to later stages of synapse assembly and refinement. Our data highlight temporal mechanisms for visual feature convergence and promote the GF circuit and the Drosophila optic glomeruli, where VPN to GF connectivity resides, as a powerful developmental model for investigating complex wiring programs and developmental plasticity.

neuroscience↗

bioRxiv2019

Protein Docking and Steered Molecular Dynamics Reveal Alternative Regulatory Sites on the SERCA Calcium Transporter

The transport activity of the calcium ATPase SERCA is modulated by an inhibitory interaction with a 52-residue transmembrane peptide, phospholamban (PLB). Biochemical and structural studies have revealed the primary inhibitory site on SERCA, but PLB has been hypothesized to interact with alternative sites on SERCA that are distinct from the inhibitory site. The present study was undertaken to test these hypotheses and explore structural determinants of SERCA regulation by PLB. Steered molecular dynamics (SMD) and membrane protein-protein docking experiments were performed to investigate the apparent affinity of PLB interactions with candidate sites on SERCA. We modeled the relative binding of PLB to several different conformations of SERCA, representing different enzymatic states sampled during the calcium transport catalytic cycle. Overall, the SMD and docking experiments suggest that the canonical binding site is preferred, but also provide evidence for alternative sites that are favorable for certain conformational states of SERCA.

biophysics↗