Actin-binding protein profilin1 is an important determinant of cellular phosphoinositide control.

التفاصيل البيبلوغرافية
العنوان:	Actin-binding protein profilin1 is an important determinant of cellular phosphoinositide control.
المؤلفون:	Ricci MMC; Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Orenberg A; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Ohayon L; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Gau D; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Wills RC; Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Bae Y; Department of Pathology and Anatomical Science, University at Buffalo, Buffalo, New York, USA., Das T; Tavotek Biotherapeutics, Spring House, Pennsylvania, USA., Koes D; Department of Computational and Systems Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Hammond GRV; Department of Cell Biology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address: ghammond@pitt.edu., Roy P; Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania, USA; Department of Pathology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. Electronic address: par19@pitt.edu.
المصدر:	The Journal of biological chemistry [J Biol Chem] 2024 Jan; Vol. 300 (1), pp. 105583. Date of Electronic Publication: 2023 Dec 21.
نوع المنشور:	Journal Article
اللغة:	English
بيانات الدورية:	Publisher: Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Country of Publication: United States NLM ID: 2985121R Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1083-351X (Electronic) Linking ISSN: 00219258 NLM ISO Abbreviation: J Biol Chem Subsets: MEDLINE
أسماء مطبوعة:	Publication: 2021- : [New York, NY] : Elsevier Inc. on behalf of American Society for Biochemistry and Molecular Biology Original Publication: Baltimore, MD : American Society for Biochemistry and Molecular Biology
مواضيع طبية MeSH:	Phosphatidylinositols/metabolism , Profilins/metabolism, Epidermal Growth Factor/metabolism ; Phosphatidylinositol 3-Kinases/metabolism ; Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases/metabolism ; Humans ; HEK293 Cells
مستخلص:	Membrane polyphosphoinositides (PPIs) are lipid-signaling molecules that undergo metabolic turnover and influence a diverse range of cellular functions. PPIs regulate the activity and/or spatial localization of a number of actin-binding proteins (ABPs) through direct interactions; however, it is much less clear whether ABPs could also be an integral part in regulating PPI signaling. In this study, we show that ABP profilin1 (Pfn1) is an important molecular determinant of the cellular content of PI(4,5)P 2 (the most abundant PPI in cells). In growth factor (EGF) stimulation setting, Pfn1 depletion does not impact PI(4,5)P 2 hydrolysis but enhances plasma membrane (PM) enrichment of PPIs that are produced downstream of activated PI3-kinase, including PI(3,4,5)P 3 and PI(3,4)P 2, the latter consistent with increased PM recruitment of SH2-containing inositol 5' phosphatase (SHIP2) (a key enzyme for PI(3,4)P 2 biosynthesis). Although Pfn1 binds to PPIs in vitro, our data suggest that Pfn1's affinity to PPIs and PM presence in actual cells, if at all, is negligible, suggesting that Pfn1 is unlikely to directly compete with SHIP2 for binding to PM PPIs. Additionally, we provide evidence for Pfn1's interaction with SHIP2 in cells and modulation of this interaction upon EGF stimulation, raising an alternative possibility of Pfn1 binding as a potential restrictive mechanism for PM recruitment of SHIP2. In conclusion, our findings challenge the dogma of Pfn1's binding to PM by PPI interaction, uncover a previously unrecognized role of Pfn1 in PI(4,5)P 2 homeostasis and provide a new mechanistic avenue of how an ABP could potentially impact PI3K signaling byproducts in cells through lipid phosphatase control. Competing Interests: Conflict of interest The authors declare that they have no conflict of interest with the contents of this article. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
معلومات مُعتمدة:	R01 CA271095 United States CA NCI NIH HHS; T32 HL076124 United States HL NHLBI NIH HHS; R21 EY032632 United States EY NEI NIH HHS; R01 CA248873 United States CA NCI NIH HHS; T32 HL129964 United States HL NHLBI NIH HHS; K99 CA267180 United States CA NCI NIH HHS
فهرسة مساهمة:	Keywords: PI(3,4)P(2); PI(3,4,5)P(3); PI(4,5)P(2); SHIP2; phosphoinositides; profilin
المشرفين على المادة:	62229-50-9 (Epidermal Growth Factor) EC 2.7.1.- (Phosphatidylinositol 3-Kinases) EC 3.1.3.86 (Phosphatidylinositol-3,4,5-Trisphosphate 5-Phosphatases) 0 (Phosphatidylinositols) 0 (Profilins) 0 (PFN1 protein, human)
تواريخ الأحداث:	Date Created: 20231223 Date Completed: 20240213 Latest Revision: 20240213
رمز التحديث:	20240214
مُعرف محوري في PubMed:	PMC10826164
DOI:	10.1016/j.jbc.2023.105583
PMID:	38141770
قاعدة البيانات:	MEDLINE

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تدمد:	1083-351X
DOI:	10.1016/j.jbc.2023.105583