ArticleProceedings of the National Academy of Sciences of the United States of America2009
Loss of phosphatidylinositol 4-kinase 2alpha activity causes late onset degeneration of spinal cord axons.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
52 citing papers in PubMed, 77 citations in OpenAlex.
- PI4K and PIPK families in breast cancer: subtype-specific oncogenic mechanisms and precision therapeutic strategies.Molecular biology reports · 2026Review
- Dampened HPG axis activity and altered ovarian gene transcription in Dummerstorf high-fertility mouse line FL2.Endocrine connections · 2026Article
- Phosphoinositide kinases in cancer: from molecular mechanisms to therapeutic opportunities.Nature reviews. Cancer · 2025Review
- Assessing the Causal Relationships Between Lipid Species and Stroke by Using Mendelian Randomization.Molecular neurobiology · 2025Article
- Phosphatidylinositol 4-phosphate; A minor lipid with multiple personalities.Biochimica et biophysica acta. Molecular and cell biology of lipids · 2025Review
- Lysosomal Repair in Health and Disease.Journal of cellular physiology · 2025Review
- Two Novel Variants inNeurology. Genetics · 2024Article
- Lysosomes in senescence and aging.EMBO reports · 2023Review
- A Plethora of Functions Condensed into Tiny Phospholipids: The Story of PI4P and PI(4,5)PCells · 2023Review
- Autophagic lysosome reformation in health and disease.Autophagy · 2023Review
- Biology of Stress Responses in Aging.Aging biology · 2023Article
- The PITT pathway: Keeping lysosomes young.Clinical and translational medicine · 2022Article
- Article
- PI4K2A deficiency causes innate error in intracellular trafficking with developmental and epileptic-dyskinetic encephalopathy.Annals of clinical and translational neurology · 2022Article
- Mouse models for hereditary spastic paraplegia uncover a role of PI4K2A in autophagic lysosome reformation.Autophagy · 2021Article
- Proteomics Profiling with SWATH-MS Quantitative Analysis of Changes in the Human Brain with HIV Infection Reveals a Differential Impact on the Frontal and Temporal Lobes.Brain sciences · 2021Article
- NPC1 regulates the distribution of phosphatidylinositol 4-kinases at Golgi and lysosomal membranes.The EMBO journal · 2021Article
- Phosphoinositides signaling modulates microglial actin remodeling and phagocytosis in Alzheimer's disease.Cell communication and signaling : CCS · 2021Review
- Novel defect in phosphatidylinositol 4-kinase type 2-alpha (PI4K2A) at the membrane-enzyme interface is associated with metabolic cutis laxa.Journal of inherited metabolic disease · 2020Article
- Pi4KIIα Regulates Unconditioned Stimulus-Retrieval-Induced Fear Memory Reconsolidation through Endosomal Trafficking of AMPA Receptors.iScience · 2020Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphoinositide (PI) lipids are intracellular membrane signaling intermediates and effectors produced by localized PI kinase and phosphatase activities. Although many signaling roles of PI kinases have been identified in cultured cell lines, transgenic animal studies have produced unexpected insight into the in vivo functions of specific PI 3- and 5-kinases, but no mammalian PI 4-kinase (PI4K) knockout has previously been reported. Prior studies using cultured cells implicated the PI4K2alpha isozyme in diverse functions, including receptor signaling, ion channel regulation, endosomal trafficking, and regulated secretion. We now show that despite these important functions, mice lacking PI4K2alpha kinase activity initially appear normal. However, adult Pi4k2a(GT/GT) animals develop a progressive neurological disease characterized by tremor, limb weakness, urinary incontinence, and premature mortality. Histological analysis of aged Pi4k2a(GT/GT) animals revealed lipofuscin-like deposition and gliosis in the cerebellum, and loss of Purkinje cells. Peripheral nerves are essentially normal, but massive axonal degeneration was found in the spinal cord in both ascending and descending tracts. These results reveal a previously undescribed role for aberrant PI signaling in neurological disease that resembles autosomal recessive hereditary spastic paraplegia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.