Biology subjects

Sepela, R. J.

Publications and source records attributed to Sepela, R. J..

3 recordsLinked to original sources

bioRxiv2025

Environmental microbiomes drive chemotactile sensation in octopus

Microbial communities coat nearly every surface in the environment and have co-existed with animals throughout evolution. Whether animals exploit omnipresent microbial cues to navigate their surroundings is not well understood. Octopuses use "taste by touch" chemotactile receptors (CRs) to explore the seafloor, but how they distinguish meaningful surfaces from the rocks and crevices they encounter is unknown. Here, we report that secreted signals from microbiomes of ecologically relevant surfaces activate CRs to guide octopus behavior. Distinct molecules isolated from specific bacterial strains located on prey or eggs bind single CRs in subtly different structural conformations to elicit distinct mechanisms of receptor activation, ion permeation and signal transduction, and maternal care and predation behavior. Thus, microbiomes on ecological surfaces act at the level of primary sensory receptors to inform behavior. Our study demonstrates that uncovering interkingdom interactions is essential to understanding how animal sensory systems evolved in a microbe rich world. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=200 SRC="FIGDIR/small/641191v1_ufig1.gif" ALT="Figure 1"> View larger version (140K): org.highwire.dtl.DTLVardef@15f365eorg.highwire.dtl.DTLVardef@1ea5606org.highwire.dtl.DTLVardef@1b5ad1aorg.highwire.dtl.DTLVardef@779e6e_HPS_FORMAT_FIGEXP M_FIG C_FIG HighlightsO_LIChemotactile receptors (CRs) detect microbiomes of prey and progeny C_LIO_LIDiverse microbial signals bind single CRs with distinct structural conformations C_LIO_LIDistinct microbial signals activate single CRs to permeate different ions C_LIO_LIEnvironmental microbes elicit octopus predatory and maternal behaviors C_LI

physiology↗

bioRxiv2021

The AMIGO1 adhesion protein modulates movement of Kv2.1 voltage sensors

Kv2 voltage-gated potassium channels are modulated by AMIGO neuronal adhesion proteins. Here, we identify steps in the conductance activation pathway of Kv2.1 channels that are modulated by AMIGO1 using voltage clamp recordings and spectroscopy of heterologously expressed Kv2.1 and AMIGO1 in mammalian cell lines. AMIGO1 speeds early voltage sensor movements and shifts the gating charge-voltage relationship to more negative voltages. The gating charge-voltage relationship indicates that AMIGO1 exerts a larger energetic effect on voltage sensor movement than apparent from the midpoint of the conductance-voltage relationship. When voltage sensors are detained at rest by voltage sensor toxins, AMIGO1 has a greater impact on the conductance-voltage relationship. Fluorescence measurements from voltage sensor toxins bound to Kv2.1 indicate that with AMIGO1, the voltage sensors enter their earliest resting conformation, yet this conformation is less stable upon voltage stimulation. We conclude that AMIGO1 modulates the Kv2.1 conductance activation pathway by destabilizing the earliest resting state of the voltage sensors. Statement of SignificanceKv2 potassium channels activate a potassium conductance that shapes neuronal action potentials. The AMIGO family of adhesion proteins modulate activation of Kv2 conductances, yet, which activation steps are modified is unknown. This study finds that AMIGO1 destabilizes the earliest resting conformation of the Kv2.1 voltage sensors to promote activation of channel conductance.

biophysics↗

bioRxiv2019

An imaging method to measure conformational changes of voltage sensors of endogenous ion channels in tissue

A primary goal of molecular physiology is to understand how conformational changes of proteins affect the function of cells, tissues, and organisms. Here, we describe an imaging method for measuring the conformational changes of the voltage sensors of endogenous ion channel proteins within live tissue, without genetic modification. We synthesized GxTX-594, a variant of the peptidyl tarantula toxin guangxitoxin-1E, conjugated to a fluorophore optimal for two-photon excitation imaging through light-scattering tissue. GxTX-594 targets the voltage sensors of Kv2 proteins, which form potassium channels and plasma membrane-endoplasmic reticulum junctions. GxTX-594 dynamically labels Kv2 proteins on cell surfaces in response to voltage stimulation. To interpret dynamic changes in labeling intensity, we developed a statistical thermodynamic model that relates the conformational changes of Kv2 voltage sensors to labeling intensity. We used two-photon excitation imaging of rat brain slices to image Kv2 proteins in neurons. This imaging method enabled identification of conformational changes of endogenous Kv2 voltage sensors in tissue.

biophysics↗