ArticleJournal of cell science2026
Molecular insights into profilin 1-dependent regulation of cellular phosphatidylinositol (4,5)-bisphosphate.
Andrew Orenberg, Michael Chirumbolo, Ian Eder, Jia-Jun Liu, Silvia Liu, David Gau, Yubo Tang, Klemens Rottner, Jianhua Luo, Gerald V Hammond and 1 more
Abstract read
In one paragraphArticle in Journal of cell science, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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1 · What the graph read from itWhat it found
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3 · Its place in the literatureWho cites it
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
11 authors.
Andrew OrenbergDepartment of Bioengineering, University of Pittsburgh, 306 CNBIO, 300 Technology Drive, Pittsburgh, PA 15219, USA.
Michael ChirumboloDepartment of Cell Biology, University of Pittsburgh, 3500 Terrace Street S362 BST (South) Pittsburgh, PA 15261, USA.ORCID 0009-0009-6445-9033 Ian EderDepartment of Cell Biology, University of Pittsburgh, 3500 Terrace Street S362 BST (South) Pittsburgh, PA 15261, USA.
Jia-Jun LiuDepartment of Pathology, University of Pittsburgh, BST, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
Silvia LiuDepartment of Pathology, University of Pittsburgh, BST, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
David GauDepartment of Pathology, University of Pittsburgh, BST, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
Yubo TangDivision of Molecular Cell Biology, Institute for Cell- and Neurobiology, Technische Universität Braunschweig, 38106 Braunschweig, Germany.ORCID 0009-0000-8813-7121 Klemens RottnerDivision of Molecular Cell Biology, Institute for Cell- and Neurobiology, Technische Universität Braunschweig, 38106 Braunschweig, Germany.ORCID 0000-0003-4244-4198 Jianhua LuoDepartment of Pathology, University of Pittsburgh, BST, 200 Lothrop Street, Pittsburgh, PA 15261, USA.
Gerald V HammondDepartment of Cell Biology, University of Pittsburgh, 3500 Terrace Street S362 BST (South) Pittsburgh, PA 15261, USA.ORCID 0000-0002-6660-3272 Partha RoyDepartment of Bioengineering, University of Pittsburgh, 306 CNBIO, 300 Technology Drive, Pittsburgh, PA 15219, USA.ORCID 0000-0002-4946-8531 Funding
Cellular Approaches to Tissue Engineering/RegenerationT32EB001026 · NIBIB · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI DUNCAN, ANDREW W, MONGA, SATDARSHAN SINGH · 2003 to 2024
$5.5MProfilin biology in breast cancerR01CA248873 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI ROY, PARTHA · 2021 to 2025
$1.8MTranscriptional Regulation of Dormancy and Emergence in Breast CancerR01CA271095 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI PARTHA ROY · 2023 to 2026
$1.5MDiscovery of Cell-based Chemical Probes Targeting Aberrant Angiogenesis in the EyeR21EY032632 · NEI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HURYN, DONNA M, KOES, DAVID RYAN · 2022 to 2023
$426kPfn1’s Role in Genomic Stability and Immune Response in Breast CancerF31CA306130 · NCI · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ian Eder · 2025 to 2026
$100kChina Scholarship CouncilDepartment of Defense HT425-24-2-0556Deutsche Forschungsgemeinschaft RO2414/8-1NCI NIH HHS F31 CA306130NCI NIH HHS R01 CA248873NCI NIH HHS R01 CA271095NEI NIH HHS R21 EY032632NIBIB NIH HHS T32 EB001026NIH HHS R01CA248873NIH HHS R01CA271095NIH HHS R21EY-032632NIH HHS T32HL076124, F31CA306130University of Pittsburgh
6 · The paper itselfAbstract
Phosphatidylinositol (4,5)-bisphosphate (PIP2), the most abundant cellular poly-phosphoinositide (PPI) class of phospholipid, is a central plasma membrane (PM)-associated signaling hub that controls many cellular processes. In this study, we demonstrate that both deletion of the gene encoding actin-binding protein profilin 1 (Pfn1) and disruption of Pfn1-actin interaction leads to downregulation of PM PIP2 content in cells. This is also phenocopied when F-actin is depolymerized, implying that Pfn1-dependent PIP2 alteration is related to its actin-regulatory function. Phospholipase C (PLC) activity is crucial for Pfn1-deficient cells to exhibit the PIP2-related phenotype. These findings, taken together with biochemical signatures of elevated PIP2 hydrolysis (higher baseline PM diacylglycerol-to PIP2 ratio and protein kinase C activity) exhibited by Pfn1-deficient cells, imply that PLC-mediated PIP2 hydrolysis plays a role in Pfn1-dependent regulation of PM PIP2. Furthermore, we unexpectedly found that Pfn1 loss leads to dramatic alterations in several other important forms of lipids, revealing a previously unrecognized role of Pfn1 as a broad regulator of cellular lipid environment that extends beyond PPI control. In conclusion, our study establishes Pfn1 as an important regulator of cellular lipid homeostasis.
Indexed as
Phosphatidylinositol 4,5-DiphosphateProfilinsActinsAnimalsCell MembraneHumansHydrolysisMiceSignal TransductionType C PhospholipasesActinsPfn1 protein, mousePhosphatidylinositol 4,5-DiphosphateProfilinsType C PhospholipasesActinDiacylglycerolHydrolysisPhospholipasePIP2Profilin 1
Identifiers
PMID42163648
PMCPMC13286375
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