Neuronal cilia in energy homeostasis

Brewer, Kathryn M.; Brewer, Katlyn K.; Richardson, Nicholas C.; Berbari, Nicolas F.

doi:10.3389/fcell.2022.1082141

Cited by 15 publications

(6 citation statements)

References 130 publications

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“…These included cilia enriched with only ARL13B (red cilia, hereafter ARL13B+), cilia enriched with only ADCY3 (green cilia, hereafter ADCY3+), and cilia localizing both ARL13B and ADCY3 (orange cilia, hereafter COLO) (Figure 2A,B) [28,36,38]. We chose to focus on several brain regions where cilia have been implicated in behaviors such as feeding and reward [39][40][41]. These brain regions include the hypothalamic nuclei, such as the arcuate nucleus (ARC), paraventricular nucleus (PVN), ventromedial hypothalamus (VMH), and suprachiasmatic nucleus (SCN), as well as the shell (NAs) and core (NAc) of the nucleus accumbens (Figure 2C).…”

Section: Approaches For Cilia Visualization and Large-scale Analysis ...mentioning

confidence: 99%

Postnatal Dynamic Ciliary ARL13B and ADCY3 Localization in the Mouse Brain

Brewer,

Terry

et al. 2024

Cells

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Primary cilia are hair-like structures found on nearly all mammalian cell types, including cells in the developing and adult brain. A diverse set of receptors and signaling proteins localize within cilia to regulate many physiological and developmental pathways, including the Hedgehog (Hh) pathway. Defects in cilia structure, protein localization, and function lead to genetic disorders called ciliopathies, which present with various clinical features that include several neurodevelopmental phenotypes and hyperphagia-associated obesity. Despite their dysfunction being implicated in several disease states, understanding their roles in central nervous system (CNS) development and signaling has proven challenging. We hypothesize that dynamic changes to ciliary protein composition contribute to this challenge and may reflect unrecognized diversity of CNS cilia. The proteins ARL13B and ADCY3 are established markers of cilia in the brain. ARL13B is a regulatory GTPase important for regulating cilia structure, protein trafficking, and Hh signaling, and ADCY3 is a ciliary adenylyl cyclase. Here, we examine the ciliary localization of ARL13B and ADCY3 in the perinatal and adult mouse brain. We define changes in the proportion of cilia enriched for ARL13B and ADCY3 depending on brain region and age. Furthermore, we identify distinct lengths of cilia within specific brain regions of male and female mice. ARL13B+ cilia become relatively rare with age in many brain regions, including the hypothalamic feeding centers, while ADCY3 becomes a prominent cilia marker in the mature adult brain. It is important to understand the endogenous localization patterns of these proteins throughout development and under different physiological conditions as these common cilia markers may be more dynamic than initially expected. Understanding regional- and developmental-associated cilia protein composition signatures and physiological condition cilia dynamic changes in the CNS may reveal the molecular mechanisms associated with the features commonly observed in ciliopathy models and ciliopathies, like obesity and diabetes.

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Section: Approaches For Cilia Visualization and Large-scale Analysis ...mentioning

confidence: 99%

Postnatal Dynamic Ciliary ARL13B and ADCY3 Localization in the Mouse Brain

Brewer,

Terry

et al. 2024

Cells

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“…While the modulation of ciliary calcium levels upon GPCR and Gq protein activation remains not well understood, activation or inhibition of ciliary adenylyl cyclases via GPCR/Gs proteins to modulate cAMP signaling has been described in more detail (Schou et al , 2015 ; Mykytyn & Askwith, 2017 ; Anvarian et al , 2019 ; Nachury & Mick, 2019 ; Barbeito et al , 2021 ; Wachten & Mick, 2021 ; Brewer et al , 2022 ; Jin & Zhong, 2022 ). Several studies have started to dissect ciliary cAMP dynamics upon ligand‐dependent GPCR activation in different cell types using genetically encoded biosensors (see below).…”

Section: The Different Levels Of Primary Cilia Dynamicsmentioning

confidence: 99%

Emerging principles of primary cilia dynamics in controlling tissue organization and function

Gopalakrishnan,

Feistel,

Friedrich

et al. 2023

The EMBO Journal

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Primary cilia project from the surface of most vertebrate cells and are key in sensing extracellular signals and locally transducing this information into a cellular response. Recent findings show that primary cilia are not merely static organelles with a distinct lipid and protein composition. Instead, the function of primary cilia relies on the dynamic composition of molecules within the cilium, the context‐dependent sensing and processing of extracellular stimuli, and cycles of assembly and disassembly in a cell‐ and tissue‐specific manner. Thereby, primary cilia dynamically integrate different cellular inputs and control cell fate and function during tissue development. Here, we review the recently emerging concept of primary cilia dynamics in tissue development, organization, remodeling, and function.

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“…Non-motile primary cilia control signaling in a wide variety of cell types [ 199 , 200 ]. Primary cilia regulate the metabolism and cell migration in neurons and the metabolism in astrocytes [ 199 , 201 , 202 ]. Moreover, primary cilia of adult neural stem cells are essential for adult neurogenesis.…”

Section: Main Textmentioning

confidence: 99%

Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases

Chu,

Xie,

Payan

et al. 2023

Mol Neurodegeneration

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The AAA+ ATPase valosin containing protein (VCP) is essential for cell and organ homeostasis, especially in cells of the nervous system. As part of a large network, VCP collaborates with many cofactors to ensure proteostasis under normal, stress, and disease conditions. A large number of mutations have revealed the importance of VCP for human health. In particular, VCP facilitates the dismantling of protein aggregates and the removal of dysfunctional organelles. These are critical events to prevent malfunction of the brain and other parts of the nervous system. In line with this idea, VCP mutants are linked to the onset and progression of neurodegeneration and other diseases. The intricate molecular mechanisms that connect VCP mutations to distinct brain pathologies continue to be uncovered. Emerging evidence supports the model that VCP controls cellular functions on multiple levels and in a cell type specific fashion. Accordingly, VCP mutants derail cellular homeostasis through several mechanisms that can instigate disease. Our review focuses on the association between VCP malfunction and neurodegeneration. We discuss the latest insights in the field, emphasize open questions, and speculate on the potential of VCP as a drug target for some of the most devastating forms of neurodegeneration.

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Neuronal cilia in energy homeostasis

Cited by 15 publications

References 130 publications

Postnatal Dynamic Ciliary ARL13B and ADCY3 Localization in the Mouse Brain

Postnatal Dynamic Ciliary ARL13B and ADCY3 Localization in the Mouse Brain

Emerging principles of primary cilia dynamics in controlling tissue organization and function

Valosin containing protein (VCP): initiator, modifier, and potential drug target for neurodegenerative diseases

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