m-Calpain is required for preimplantation embryonic development in mice

Dutt, Previn; Croall, Dorothy E.; Arthur, J. Simon C.; Veyra, Teresa De; Williams, Karen; Elce, John S.; Greer, Peter A.

doi:10.1186/1471-213x-6-3

Cited by 135 publications

(51 citation statements)

References 49 publications

(58 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Knock-out of the -calpain large subunit, calpain 1, results in viable mice with reduced platelet aggregation and impaired tyrosine phosphorylation in platelets, but not overt phenotype (11). Knock-out of the m-calpain large subunit, calpain 2, or of calpain small subunit 1 (CSS1) is embryonically lethal (12)(13)(14).Both m-and -calpains are considered to be cytosolic enzymes (2,3, 15,16). An association of m-and -calpains with subcellular organelles including endoplasmic reticulum and Golgi apparatus has been observed, but this association is hydrophobic, and the calpains are largely localized to the cytoplasmic surface of the organelle membranes (17-19).…”

mentioning

confidence: 99%

See 1 more Smart Citation

N Terminus of Calpain 1 Is a Mitochondrial Targeting Sequence

Badugu

Garcia

Bondada

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

The ubiquitous m-and -calpains are thought to be localized in the cytosolic compartment, as is their endogenous inhibitor calpastatin. Previously, -calpain was found to be enriched in mitochondrial fractions isolated from rat cerebral cortex and SH-SY5Y neuroblastoma cells, but the submitochondrial localization of -calpain was not determined. In the present study, submitochondrial fractionation and digitonin permeabilization studies indicated that both calpain 1 and calpain small subunit 1, which together form -calpain, are present in the mitochondrial intermembrane space. The N terminus of calpain 1 contains an amphipathic ␣-helical domain, and is distinct from the N terminus of calpain 2. Calpain 1, but not calpain 2, was imported into mitochondria. Removal of the N-terminal 22 amino acids of calpain 1 blocked the mitochondrial calpain import, while addition of this N-terminal region to calpain 2 or green fluorescent protein enabled mitochondrial import. The N terminus of calpain 1 was not processed following mitochondrial import, but was removed by autolysis following calpain activation. Calpain small subunit 1 was not directly imported into mitochondria, but was imported in the presence of calpain 1. The presence of a mitochondrial targeting sequence in the N-terminal region of calpain 1 is consistent with the localization of -calpain to the mitochondrial intermembrane space and provides new insight into the possible functions of this cysteine protease.Calpains (EC 3.4.22.17) are a family of Ca 2ϩ -activated cysteine proteases, including both ubiquitous and tissue-specific isoforms, that cleave their substrate proteins at discrete sites to modulate activity (1-3). The best characterized, and the predominant calpains in the central nervous system, are the classical m-and -calpains. Their physiological roles have not been fully elucidated but include cell motility, cell differentiation, membrane fusion, platelet activation, and signal transduction (3). Also extensively investigated have been the pathological roles of calpains in cell death, where calpains can cleave key structural proteins and contribute to the release of death-related proteins such as apoptosis-inducing factor (AIF) 3 (4 -9). At present, it is unclear whether the -and m-calpains have distinct or overlapping functions. They are each heterodimers consisting of a unique 80-kDa large catalytic subunit (calpain 1 or 2) and a common 28-kDa small regulatory subunit (calpain small subunit 1 or 2) (2). In vitro, the substrates of m-and -calpains are similar, if not identical (10). Knock-out of the -calpain large subunit, calpain 1, results in viable mice with reduced platelet aggregation and impaired tyrosine phosphorylation in platelets, but not overt phenotype (11). Knock-out of the m-calpain large subunit, calpain 2, or of calpain small subunit 1 (CSS1) is embryonically lethal (12)(13)(14).Both m-and -calpains are considered to be cytosolic enzymes (2,3, 15,16). An association of m-and -calpains with subcellular organelles including endoplasmic ret...

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

N Terminus of Calpain 1 Is a Mitochondrial Targeting Sequence

Badugu

Garcia

Bondada

et al. 2008

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Thus, the genetic knockout approach can demonstrate the role of individual calpains in vivo. Both CAPN2 (18) and Capns1 (3) knockout mouse are embryonic lethal. In contrast, the CAPN1 null mice are viable and have normal theta burst-evoked LTP and fear conditioning learning (24).…”

Section: Discussionmentioning

confidence: 99%

Calpain 2 Activated through N-Methyl-d-Aspartic Acid Receptor Signaling Cleaves CPEB3 and Abrogates CPEB3-Repressed Translation in Neurons

Wang

Huang

2012

Molecular and Cellular Biology

View full text Add to dashboard Cite

b Long-term memory requires the activity-dependent reorganization of the synaptic proteome to modulate synaptic efficacy and consequently consolidate memory. Activity-regulated RNA translation can change the protein composition at the stimulated synapse. Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein that represses translation of its target mRNAs in neurons, while activation of N-methyl-D-aspartic acid (NMDA) receptors alleviates this repression. Although recent research has revealed the mechanism of CPEB3-inhibited translation, how NMDA receptor signaling modulates the translational activity of CPEB3 remains unclear. This study shows that the repressor CPEB3 is degraded in NMDA-stimulated neurons and that the degradation of CPEB3 is accompanied by the elevated expression of CPEB3's target, epidermal growth factor receptor (EGFR), mostly at the translational level. Using pharmacological and knockdown approaches, we have identified that calpain 2, activated by the influx of calcium through NMDA receptors, proteolyzes the N-terminal repression motif but not the C-terminal RNA-binding domain of CPEB3. As a result, the calpain 2-cleaved CPEB3 fragment binds to RNA but fails to repress translation. Therefore, the cleavage of CPEB3 by NMDA-activated calpain 2 accounts for the activityrelated translation of CPEB3-targeted RNAs. Synaptic plasticity, which is the ability of neuronal synapses to undergo morphological and functional changes in response to various stimuli, forms the underlying molecular basis of memory. Activity-induced plasticity-related protein (PRP) synthesis sustains long-lasting synapse changes that are crucial for establishing and consolidating long-term memory. Neurons employ three strategies to increase the synaptic levels of specific PRPs upon activation. PRPs are deposited at the stimulated synapses by capturing the trafficking molecules in the form of proteins or RNAs de novo synthesized from soma (20, 51). The newly delivered PRP RNAs are then translated locally at synapses (51). Alternatively, PRPs are produced through translational activation of preexisting dendritic dormant mRNAs (10,13,45). RNA-binding proteins play essential roles in the modulation of PRP production by regulating dendritic RNA transport, translation, and/or degradation (10,13,22,45). Cytoplasmic polyadenylation element-binding protein 3 (CPEB3) is a sequence-specific RNA-binding protein in vertebrates that likely influences PRP synthesis and memory function for the following reasons. First, the Drosophila melanogaster homologue of CPEB3, Orb2, is required for the long-term conditioning of male courtship behavior (32). Clinical research has shown that a single-nucleotide polymorphism (SNP) (a T-to-C substitution) in intron 3 of CPEB3 gene affects human episodic memory. Homozygous carriers of the C allele of SNP have poorer performance in the delayed verbal memory recall tests (56). This C allele of SNP located in the CPEB3 ribozyme sequence, exhibits more than 2-fold ...

show abstract

“…The calpains are thus probably necessary in all the stages of cell life. Calpain genes were particularly indispensable for early development of vertebrates [10][11][12][13]. The CAPN1 (NP_ 001080485.1) distribution was performed during the development of Xenopus laevis and its essential role demonstrated [14].…”

Section: Introductionmentioning

confidence: 99%

Expression Patterns of CAPN1 and CAPN8b Genes during Embryogenesis in Xenopus laevis

Abrouk-Vérot¹,

Brun²,

Exbrayat³

2013

CellBio

View full text Add to dashboard Cite

Calpains are a superfamily of Ca 2+ -dependent cysteine proteases, implicated in various cellular processes and thus probably necessary in all the stages of cell life. The first extended report of quantification of total RNAs within the developmental stages of Xenopus laevis was described in this study. Decreases of total RNAs were positively associated with waves of apoptotic cell death (onset of gastrulation, and morphogenesis). Using qPCR, the temporal expression pattern of CAPN1 and CPAN8b (XCL-2) were characterized during the Xenopus laevis embryogenesis. Transcripts of the CAPN1 and CAPN8 genes were detectable from gastrula stage and their levels oscillated throughout development. The expression of the CAPN1 (mu/I) gene was observed in earliest stage, indicating a maternal origin, while expression of the CAPN8b gene was detectable after midblastula transition. The levels of the two transcripts then started to rise again obviously as a result of zygotic expression (stage 11). The CAPN1 gene expression was particularly expressed at tailbud stage, while the CAPN8 transcripts were found at gastrula, neurula and tailbud stages. This is the first report of quantification of mRNAs CAPN8b and CAPN1 (mu/I) within the developmental stages of Xenopus laevis by qPCR.

show abstract

m-Calpain is required for preimplantation embryonic development in mice

Cited by 135 publications

References 49 publications

N Terminus of Calpain 1 Is a Mitochondrial Targeting Sequence

N Terminus of Calpain 1 Is a Mitochondrial Targeting Sequence

Calpain 2 Activated through N-Methyl-d-Aspartic Acid Receptor Signaling Cleaves CPEB3 and Abrogates CPEB3-Repressed Translation in Neurons

Expression Patterns of CAPN1 and CAPN8b Genes during Embryogenesis in Xenopus laevis

Contact Info

Product

Resources

About