Superresolution Microscopy Reveals Distinct Phosphoinositide Subdomains Within the Cilia Transition Zone

Conduit, Sarah E; Davies, Elizabeth M.; Fulcher, Alex J.; Oorschot, Viola; Mitchell, Christina A.

doi:10.3389/fcell.2021.634649

Cited by 22 publications

(18 citation statements)

References 64 publications

(168 reference statements)

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“…Previous results have shown that INPP5E is concentrated at the cilia base, where it helps control phosphoinositide metabolism (43). Primary cilia are present on virtually all cell types.…”

Section: Discussionmentioning

confidence: 99%

Identifying Environmental Endocrine Disruptors Associated With the Age at Menarche by Integrating a Transcriptome-Wide Association Study With Chemical-Gene-Interaction Analysis

Feng

Qin

et al. 2022

Front. Endocrinol.

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Menarche is the first occurrence of menstrual bleeding and one of the most important events of female puberty. Alarmingly, over the last several decades, the mean age at menarche (AAM) has decreased. Environmental endocrine disruptors (EEDs) are chemicals that may interfere with the endocrine system, resulting in adverse developmental, immunological, neurological, and reproductive effects in humans. Thus, the effects of EEDs on fertility and reproduction are growing concerns in modern societies. In this study, we aimed to determine the influence of genetic and environmental factors on AAM. We used data from an AAM genome-wide association study of 329,345 women to conduct a transcriptome-wide association study (TWAS) with FUSION software. As references, we determined the gene-expression levels in the hypothalamus, pituitary gland, ovaries, uterus, and whole blood. We performed Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses using the significantly dysregulated genes identified by the TWAS. Using the STRING database, we also generated a protein–protein-interaction network to analyze common AAM-specific genes identified by the TWAS with different tissues. We performed chemical-related gene set enrichment analysis (CGSEA) and identified significant TWAS genes to uncover relationships between different chemicals and AAM. The TWAS identified 9,848 genes; among these, 1580 genes were significant (P < 0.05), and 11 genes were significant among the hypothalamus, pituitary, ovary, uterus, and whole blood. CGSEA identified 1,634 chemicals, including 120 chemicals significantly correlated with AAM. In summary, we performed a TWAS (for genetic factors) and CGSEA (for environmental factors) focusing on AAM and identified several AAM-associated genes and EEDs. The results of this study expand our understanding of genetic and environmental factors related to the onset of female puberty.

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“…Previous results have shown that INPP5E is concentrated at the cilia base, where it helps control phosphoinositide metabolism (43). Primary cilia are present on virtually all cell types.…”

Section: Discussionmentioning

confidence: 99%

Identifying Environmental Endocrine Disruptors Associated With the Age at Menarche by Integrating a Transcriptome-Wide Association Study With Chemical-Gene-Interaction Analysis

Feng

Qin

et al. 2022

Front. Endocrinol.

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“…A loss of INPP5e activity reduced the oncogenic Shh signalling and proliferation of medulloblastoma cells (Conduit et al, 2017). PI(3,4,5)P 3 is enriched in a ring-like subdomain exclusive from that of PI(4,5)P 2 at the ciliary TZ (Conduit et al, 2021).…”

Section: Phosphoinositidesmentioning

confidence: 99%

“…A loss of INPP5e activity reduced the oncogenic Shh signalling and proliferation of medulloblastoma cells (Conduit et al, 2017). PI(3,4,5)P 3 is enriched in a ring‐like subdomain exclusive from that of PI(4,5)P 2 at the ciliary TZ (Conduit et al, 2021). The delivery of INPP5e through Arl13b restricts PI(3,4,5)P 3 levels in the cilia of projection neurons and regulates PI3K/Akt‐mediated neural development and differentiation (Humbert et al, 2012).…”

Section: Ciliary Lipids—composition and Local Modificationmentioning

confidence: 99%

Ciliary membrane, localised lipid modification and cilia function

Dutta

Ray

2022

Journal Cellular Physiology

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Cilium, a tiny microtubule‐based cellular appendage critical for cell signalling and physiology, displays a large variety of receptors. The composition and turnover of ciliary lipids and receptors determine cell behaviour. Due to the exclusion of ribosomal machinery and limited membrane area, a cilium needs adaptive logistics to actively reconstitute the lipid and receptor compositions during development and differentiation. How is this dynamicity generated? Here, we examine whether, along with the Intraflagellar‐Transport, targeted changes in sector‐wise lipid composition could control the receptor localisation and functions in the cilia. We discuss how an interplay between ciliary lipid composition, localised lipid modification, and receptor function could contribute to cilia growth and signalling. We argue that lipid modification at the cell‐cilium interface could generate an added thrust for a selective exchange of membrane lipids and the transmembrane and membrane‐associated proteins.

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“…As an inositol polyphosphate 5-phosphatase, INPP5E is mainly located in cilia in quiescent cells to maintain it is function and stability ( Conduit et al, 2021 ; Kosling et al, 2018 ). A portion of INPP5E is also located in the lysosome, and its membrane anchoring and enzymatic activity are necessary for autophagy ( Hasegawa et al, 2016 ; Sierra Potchanant et al, 2017 ).…”

Section: Cilia Associated Cellular Signallingmentioning

confidence: 99%

INPP5E and Coordination of Signaling Networks in Cilia

Zhang

Tang²,

et al. 2022

Front. Mol. Biosci.

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Primary cilia are ubiquitous mechanosensory organelles that specifically coordinate a series of cellular signal transduction pathways to control cellular physiological processes during development and in tissue homeostasis. Defects in the function or structure of primary cilia have been shown to be associated with a large range of diseases called ciliopathies. Inositol polyphosphate-5-phosphatase E (INPP5E) is an inositol polyphosphate 5-phosphatase that is localized on the ciliary membrane by anchorage via its C-terminal prenyl moiety and hydrolyzes both phosphatidylinositol-4, 5-bisphosphate (PtdIns(4,5)P2) and PtdIns(3,4,5)P3, leading to changes in the phosphoinositide metabolism, thereby resulting in a specific phosphoinositide distribution and ensuring proper localization and trafficking of proteins in primary cilia. In addition, INPP5E also works synergistically with cilia membrane-related proteins by playing key roles in the development and maintenance homeostasis of cilia. The mutation of INPP5E will cause deficiency of primary cilia signaling transduction, ciliary instability and ciliopathies. Here, we present an overview of the role of INPP5E and its coordination of signaling networks in primary cilia.

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Superresolution Microscopy Reveals Distinct Phosphoinositide Subdomains Within the Cilia Transition Zone

Cited by 22 publications

References 64 publications

Identifying Environmental Endocrine Disruptors Associated With the Age at Menarche by Integrating a Transcriptome-Wide Association Study With Chemical-Gene-Interaction Analysis

Identifying Environmental Endocrine Disruptors Associated With the Age at Menarche by Integrating a Transcriptome-Wide Association Study With Chemical-Gene-Interaction Analysis

Ciliary membrane, localised lipid modification and cilia function

INPP5E and Coordination of Signaling Networks in Cilia

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