A5102744148- Calpain Protease Function and Regulation
- Muscle Physiology and Disorders
- Hereditary Neurological Disorders
- Meat and Animal Product Quality
- RNA regulation and disease
- Signaling Pathways in Disease
- Connexins and lens biology
- Toxoplasma gondii Research Studies
- Hippo pathway signaling and YAP/TAZ
- Nerve injury and regeneration
- Genetic Neurodegenerative Diseases
- Cardiomyopathy and Myosin Studies
- Venomous Animal Envenomation and Studies
- Peroxisome Proliferator-Activated Receptors
- Zebrafish Biomedical Research Applications
- Muscle metabolism and nutrition
- Neurobiology and Insect Physiology Research
- Atherosclerosis and Cardiovascular Diseases
- Identification and Quantification in Food
- Plant biochemistry and biosynthesis
- Endoplasmic Reticulum Stress and Disease
- Silk-based biomaterials and applications
- Retinal Development and Disorders
- Ubiquitin and proteasome pathways
- Adipose Tissue and Metabolism
Tokyo Metropolitan Institute of Medical Science
2012-2025
Advanced Research Projects Agency - Energy
2016
Tokyo Medical and Dental University
2014
The University of Tokyo
2001-2004
Limb-girdle muscular dystrophy type 2A (LGMD2A) is a genetic disease that caused by mutations in the calpain 3 gene (CAPN3), which encodes skeletal muscle-specific calpain, (also known as p94). However, precise mechanism p94 functions pathogenesis of this remains unclear. Here, using knockin mice (termed herein p94KI mice) endogenous was replaced with proteolytically inactive but structurally intact p94:C129S mutant protein, we have demonstrated stretch-dependent distribution sarcomeres...
Calpains constitute a superfamily of Ca2+-dependent cysteine proteases, indispensable for various cellular processes. Among the 15 mammalian calpains, calpain 8/nCL-2 and 9/nCL-4 are predominantly expressed in gastrointestinal tract restricted to gastric surface mucus (pit) cells stomach. Possible functions reported 8 vesicle trafficking between ER Golgi, 9 implicated suppressing tumorigenesis. These highlight that calpains regulated differently from each other conventional and, thus, have...
The precise regulation of numbers and types neurons through control cell cycle exit terminal differentiation is an essential aspect neurogenesis. Hippo signaling pathway has recently been identified as playing a crucial role in promoting multiple stem cells, including retinal progenitor cells. When activated, the core Mst1/2 kinases activate Lats1/2 kinases, which turn phosphorylate inhibit transcriptional cofactor Yap. During mouse retinogenesis, overexpression Yap prolongs proliferation,...
Calpains are Ca2+-dependent modulator Cys proteases that have a variety of functions in almost all eukaryotes. There more than 10 well-conserved mammalian calpains, among which eutherian calpain-6 (CAPN6) is unique it has amino acid substitutions at the active-site residue (to Lys humans), strongly suggesting loss proteolytic activity. CAPN6 expressed predominantly embryonic muscles, placenta, and several cultured cell lines. We previously reported involved regulating microtubule dynamics...
Calpains are intracellular Ca(2+)-regulated cysteine proteases that essential for various cellular functions. Mammalian conventional calpains (calpain-1 and calpain-2) modulate the structure function of their substrates by limited proteolysis. Thus, it is critically important to determine site(s) in proteins at which cleave. However, calpains' substrate specificity remains unclear, because amino acid (aa) sequences around cleavage sites very diverse. To clarify specificities, 84 20-mer...
ABSTRACT Introduction A 20 kDa fragment at the N‐terminus of titin is highly excreted in urine patients with Duchenne muscular dystrophy (DMD), making a prominent biomarker for muscle breakdown. This N‐terminal presumed to be product degradation by protein‐degrading enzyme, calpain 3; however, whether 3 required remains unclear. We aimed determine elevation occurs absence 3. Methods measured ELISA two genetically confirmed limb‐girdle type R1(LGMDR1) patients, 11 other LGMD and five healthy...
Because intracellular [Na(+)] is kept low by Na(+)/K(+)-ATPase, Na(+) dependence generally considered a property of extracellular enzymes. However, we found that p94/calpain 3, skeletal-muscle-specific member the Ca(2+)-activated "modulator proteases" responsible for limb-girdle muscular dystrophy ("calpainopathy"), underwent Na(+)-dependent, but not Cs(+)-dependent, autolysis in absence Ca(2+). Furthermore, and Ca(2+) complementarily activated p94 at physiological concentrations. By...
Inhibition of calpain 9, a key mediator myofibroblast differentiation and tissue fibrosis, protects against fibrosis in preclinical models.
Macrophages contribute to the development of atherosclerosis through pinocytotic deposition native LDL-derived cholesterol in macrophages vascular wall. Inhibiting macrophage-mediated lipid may have protective effects atheroprone vasculature, and identifying mechanisms that potentiate this process inform potential therapeutic interventions for atherosclerosis. Here, we report dysregulation exon junction complex-driven (EJC-driven) mRNA splicing confers hyperpinocytosis during atherogenesis....
Calpain, a Ca 2+ ‐dependent cytosolic cysteine protease, proteolytically modulates specific substrates involved in ‐mediated intracellular events, such as signal transduction, cell cycle, differentiation, and apoptosis. The 3D structure of m‐calpain, the absence , revealed that two subdomains (domains IIa IIb) protease domain (II) have an ‘open’ conformation, probably due to interactions with other domains. Although presence EF‐hand was once predicted domain, no explicit ‐binding identified...
Calpains constitute a family of intracellular Ca(2+)-regulated cysteine proteases that are indispensable in the regulation wide variety cellular functions. The improper activation calpain causes lethality or various disorders, such as muscular dystrophies and tumor formation. nCL-2/calpain 8 is predominantly expressed stomach, where it appears to be involved membrane trafficking gastric surface mucus cells (pit cells). Although primary structure nCL-2 quite similar ubiquitous m-calpain large...
Calpain is a Ca2+-regulated cytosolic protease. Mammals have 14 calpain genes, half of which are predominantly expressed in specific organ(s); the rest ubiquitously. A defect calpains causes lethality/pathogenicity, indicating their physiological indispensability. nCL-2/calpain-8a was identified as stomach-specific calpain, whose functions unclear. To elucidate these, we characterized nCL-2 detail. Unexpectedly, localized strictly to surface mucus cells gastric epithelium and mucus-secreting...
Abstract Calpain-1 and calpain-2 are highly structurally similar isoforms of calpain. The calpains, a family intracellular cysteine proteases, cleave their substrates at specific sites, thus modifying properties such as function or activity. These have long been considered to in redundant complementary manner, they both ubiquitously expressed activated Ca2+- dependent manner. However, studies using isoform-specific knockout knockdown strategies revealed that each calpain species carries out...
Calpain-3 (CAPN3), a 94-kDa member of the calpain protease family, is abundant in skeletal muscle. Mutations CAPN3 gene cause limb girdle muscular dystrophy type 2A, indicating that plays important roles muscle physiology. has several unique features. A crystallographic study revealed its C-terminal penta–EF-hand domains form homodimer, suggesting functions as homodimeric protease. To analyze complex formation more convenient manner, we performed blue native polyacrylamide gel...