ArticleThe Journal of biological chemistry2008
Phosphoinositide binding to the substrate regulates susceptibility to proteolysis by calpain.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Structural and functional insights into α-actinin isoforms and their implications in cardiovascular disease.The Journal of general physiology · 2025Review
- Proteolytic degradation of atrial sarcomere proteins underlies contractile defects in atrial fibrillation.American journal of physiology. Heart and circulatory physiology · 2024Article
- Actin Bundles Dynamics and Architecture.Biomolecules · 2023Review
- The Importance of Alpha-Actinin Proteins in Platelet Formation and Function, and Their Causative Role in Congenital Macrothrombocytopenia.International journal of molecular sciences · 2021Review
- Article
- Calpain fosters the hyperexcitability of motoneurons after spinal cord injury and leads to spasticity.eLife · 2019Article
- Focal segmental glomerulosclerosis ACTN4 mutants binding to actin: regulation by phosphomimetic mutations.Scientific reports · 2019Article
- Filopodia and focal adhesions: An integrated system driving branching morphogenesis in neuronal pathfinding and angiogenesis.Developmental biology · 2019Review
- Tyro3-mediated phosphorylation of ACTN4 at tyrosines is FAK-dependent and decreases susceptibility to cleavage by m-Calpain.The international journal of biochemistry & cell biology · 2018Article
- The fifth sense: Mechanosensory regulation of alpha-actinin-4 and its relevance for cancer metastasis.Seminars in cell & developmental biology · 2017Review
- Tadalafil Treatment Delays the Onset of Cardiomyopathy in Dystrophin-Deficient Hearts.Journal of the American Heart Association · 2016Article
- Calpain-3-mediated regulation of the Na⁺-Ca²⁺ exchanger isoform 3.Pflugers Archiv : European journal of physiology · 2016Article
- Bacterial calpains and the evolution of the calpain (C2) family of peptidases.Biology direct · 2015Article
- The role of alpha-actinin-4 in human kidney disease.Cell & bioscience · 2015Article
- α-Actinin-4 is required for amoeboid-type invasiveness of melanoma cells.The Journal of biological chemistry · 2014Article
- The carboxyl tail of alpha-actinin-4 regulates its susceptibility to m-calpain and thus functions in cell migration and spreading.The international journal of biochemistry & cell biology · 2013Article
- Integrin-dependent force transmission to the extracellular matrix by α-actinin triggers adhesion maturation.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Calpain cleaves methionine aminopeptidase-2 in a rat model of ischemia/reperfusion.Brain research · 2013Article
- Modeling the assembly of the multiple domains of α-actinin-4 and its role in actin cross-linking.Biophysical journal · 2013Article
- Alpha-actinin 4 and tumorigenesis of breast cancer.Vitamins and hormones · 2013Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Calpain-mediated proteolysis regulates cytoskeletal dynamics and is altered during aging and the progression of numerous diseases or pathological conditions. Although several cytoskeletal proteins have been identified as substrates, how localized calpain activity is regulated and the mechanisms controlling substrate recognition are not clear. In this study, we report that phosphoinositide binding regulates the susceptibility of the cytoskeletal adhesion protein alpha-actinin to proteolysis by calpains 1 and 2. At first, alpha-actinin did not appear to be a substrate for calpain 2; however, phosphatidylinositol 3,4,5-trisphosphate (PtdIns(3,4,5)P(3)) binding to alpha-actinin resulted in nearly complete proteolysis of the full-length protein, producing stable breakdown products. Calpain 1 was able to cleave alpha-actinin in the absence of phosphoinositide binding; however, PtdIns(3,4,5)P(3) binding increased the rate of proteolysis, and phosphatidylinositol 4,5-diphosphate (PtdIns(4,5)P(2)) binding significantly inhibited cleavage. Phosphoinositide binding appeared to regulate calpain proteolysis of alpha-actinin by modulating the exposure of a highly sensitive cleavage site within the calponin homology 2 domain. In U87MG glioblastoma cells, which contain elevated levels of PtdIns(3,4,5)P(3), alpha-actinin colocalized with calpain within dynamic actin cytoskeletal structures. Furthermore, proteolysis of alpha-actinin producing stable breakdown products was observed in U87MG cells treated with calcium ionophore to activate the calcium-dependent calpains. Additional evidence of PtdIns(3,4,5)P(3)-mediated calpain proteolysis of alpha-actinin was observed in rat embryonic fibroblasts. These results suggest that PtdIns(3,4,5)P(3) binding is a critical determinant for alpha-actinin proteolysis by calpain. In conclusion, phosphoinositide binding to the substrate is a potential mechanism for regulating susceptibility to proteolysis by calpain.
Indexed as
Identifiers
What OpenQuestion holds
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.