GABA-induced Ca2+signaling in the primary cilium of neurons

2025 · doi:10.1101/2025.05.26.656109
preprint OA: closed CC-BY-NC-ND-4.0
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⚙ AI-generated summary by claude@2026-07, 2026-07-17 ⓘ

Metabotropic GABA receptor subtype 1 localizes to primary cilia of mouse neurons and initiates ciliary calcium signaling, demonstrating a distinct excitatory role for GABA in this organelle.

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⚙ AI-generated deep summary by claude@2026-07, 2026-07-17 · read from full text ⓘ

The study investigates how metabotropic GABA receptor subtype 1 (GABAB1) functions within the primary cilium of neurons, asking whether this neuronal organelle acts as an autonomous compartment for signaling. Using mouse brain neurons, the authors report that GABAB1 localizes to primary cilia across multiple brain regions and that receptor activation triggers Ca2+ signaling that is restricted to the cilium. They find that this GABA-driven signaling is excitatory in the ciliary compartment, contrasting with GABA’s inhibitory effects in other neuronal domains. The main caveat is that the paper does not establish downstream functional outcomes beyond ciliary Ca2+ signaling. The paper does not explicitly discuss endometriosis or adenomyosis; it was included in the corpus via a keyword match in the upstream search index.

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Abstract

ABSTRACT The complex signaling processing in neurons requires establishment of autonomous compartments. The compartment that is unique for neurons and crucial for neuron-neuron signaling is the synapse. Another compartment, that neurons share with all other cells in the body, is the primary cilium. The primary cilium is a solitary organelle, present in almost every neuronal cell type, that extends into the extracellular space for detection of signals. Several GPCRs have been identified as ciliary receptors, and here we show that the metabotropic GABA receptor subtype 1 localizes to primary cilia of neurons across different regions of the mouse brain and that activation of these receptors initiates Ca 2+ signaling that is restricted to this organelle. The excitatory nature of GABAergic signaling in primary cilia is opposite to GABA action in other neuronal domains, indicating distinct modes of action of this universal inhibitory neurotransmitter even within the same neuron.
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ABSTRACT The complex signaling processing in neurons requires establishment of autonomous compartments. The compartment that is unique for neurons and crucial for neuron-neuron signaling is the synapse. Another compartment, that neurons share with all other cells in the body, is the primary cilium. The primary cilium is a solitary organelle, present in almost every neuronal cell type, that extends into the extracellular space for detection of signals. Several GPCRs have been identified as ciliary receptors, and here we show that the metabotropic GABA receptor subtype 1 localizes to primary cilia of neurons across different regions of the mouse brain and that activation of these receptors initiates Ca2+ signaling that is restricted to this organelle. The excitatory nature of GABAergic signaling in primary cilia is opposite to GABA action in other neuronal domains, indicating distinct modes of action of this universal inhibitory neurotransmitter even within the same neuron. Competing Interest Statement The authors have declared no competing interest.

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europepmc
last seen: 2026-05-20T01:45:00.602351+00:00
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License: CC-BY-NC-ND-4.0