Ca2+/CaM binding to CaMKI promotes IMA-3 importin binding and nuclear translocation in sensory neurons to control behavioral adaptation

Abstract

Sensory and behavioral plasticity are essential for animals to thrive in changing environments. As key effectors of intracellular calcium signaling, Ca2+/calmodulin-dependent protein kinases (CaMKs) can bridge neural activation with the many regulatory processes needed to orchestrate sensory adaptation, including by relaying signals to the nucleus. Here, we elucidate the molecular mechanism controlling the cell activation-dependent nuclear translocation of CMK-1, the Caenorhabditis elegans ortholog of mammalian CaMKI/IV, in thermosensory neurons in vivo. We show that an intracellular Ca2+ concentration elevation is necessary and sufficient to favor CMK-1 nuclear import. The binding of Ca2+/CaM to CMK-1 increases its affinity for IMA-3 importin, causing a redistribution with a relatively slow kinetics, matching the timescale of sensory adaptation. Furthermore, we show that this mechanism enables the encoding of opposite nuclear signals in neuron types with opposite calcium-responses and that it is essential for experience-dependent behavioral plasticity and gene transcription control in vivo. Since CaMKI/IV are conserved regulators of adaptable behaviors, similar mechanisms could exist in other organisms and for other sensory modalities.

Multisite gating in tonic sensory circuits integrates multimodal context to control persistent behavioral states

“…Calcium imaging experiments in AFD and FLP were performed in a temperature-controlled environment and analysed as previously described (Ippolito et al, 2021; Saro et al, 2020). YFP/CFP ratio of a YC2.3 cameleon indicator was used to compare resting calcium levels across conditions, as well as relative changes in response to short-lasting stimuli.…”

“…dg88 [slot2 Entry TeTxcds] (aka pWD157) was a gift of Wayne Davis. The generation of dg651 [slot2 Entry egl-13NLS::wrmScarlet], of dg353 [slot2 Entry mNeongreen cds] and dg650 [slot2 Entry NLS_ceBFPcds] were described in (Marques et al, 2019), (Hostettler et al, 2017) and (Ippolito et al, 2021) respectively.…”

“…Blocking synaptic transmission from AFD using Tetanus toxin also abolished the backward frequency and tail bending modulation (Fig 4B and S4B), confirming the importance of neurotransmission from AFD for warming-evoked scanning entry. AFD neurons can encode thermal history as absolute intracellular calcium levels and simultaneously respond to short-lasting thermosensory inputs with fast-adapting calcium transients (Glauser, 2022;Hawk et al, 2018;Ippolito et al, 2021). To investigate if AFD calcium dynamics could encode information of behavioral state transition, we imaged AFD calcium levels using a ratiometric YC2.3 calcium sensor and compared animals grown at 15°, grown at 25° or exposed to warming (15 to 25°C shift).…”

“…Animals already present at the region of success before dropping the food were discarded from the analysis. Fraction of successful food search was calculated using the following formula: Fraction of successful food search = Worms in region of success/Total number of worms Calcium imaging Calcium imaging experiments in AFD and FLP were performed in a temperature-controlled environment and analysed as previously described (Ippolito et al, 2021;Saro et al, 2020). YFP/CFP ratio of a YC2.3 cameleon indicator was used to compare resting calcium levels across conditions, as well as relative changes in response to short-lasting stimuli.…”

“…Primer sequences were the following: The generation of dg68 [slot1 Entry mec-3p] was previously described (Schild et al, 2014). (Marques et al, 2019), (Hostettler et al, 2017) and (Ippolito et al, 2021) respectively.…”