RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response

Konopacka, Agnieszka; Greenwood, Mingkwan; Loh, Su Yi; Paton, Julian F. R.; Murphy, David

doi:10.7554/elife.09656

Cited by 17 publications

(44 citation statements)

References 44 publications

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“…Medium and NGF were replaced every 2 d. At day 4 of NGF treatment, Caprin2 shRNA lentivirus was added to the medium, with a scrambled shRNA lentivirus being used as a control. Lentiviral vectors containing shRNA of Caprin2 and scrambled shRNA control were produced as previously described (Konopacka et al, 2015). For overexpression studies of Caprin2 in PC12 cells, an adenovirus expressing full-length Caprin2 cDNA (Konopacka et al, 2015) was used, with an eGFP -expressing virus as a control.…”

Section: Methodsmentioning

confidence: 99%

“…Lentiviral vectors containing shRNA of Caprin2 and scrambled shRNA control were produced as previously described (Konopacka et al, 2015). For overexpression studies of Caprin2 in PC12 cells, an adenovirus expressing full-length Caprin2 cDNA (Konopacka et al, 2015) was used, with an eGFP -expressing virus as a control. Production of adenoviral vectors has been described (Greenwood et al, 2015).…”

Section: Methodsmentioning

confidence: 99%

“…We then manipulated the expression of nodal gene Caprin2 in differentiated PC12 cells using lentiviral vectors that express either an shRNA specific for all splice isoforms of Caprin2 (Konopacka et al, 2015) to knockdown endogenous expression (Fig. 6 A ), or an Adenoviral vector expressing full-length rat Caprin2 cDNA (Konopacka et al, 2015) to elicit overexpression (Fig.…”

Section: Significance Testing Of Microarray Datamentioning

confidence: 99%

“…6 A ), or an Adenoviral vector expressing full-length rat Caprin2 cDNA (Konopacka et al, 2015) to elicit overexpression (Fig. 6 B ).…”

Section: Significance Testing Of Microarray Datamentioning

confidence: 99%

“…From the derived Glasso network, we identified a hub nodal gene, Caprin2 , that encodes an RNA-binding protein that we have previously identified as being important in the central osmotic defense response (Konopacka et al, 2015). To test this prediction from the Glasso algorithm, we perturbed the network in vitro by manipulating Caprin2 expression.…”

Section: Introductionmentioning

confidence: 99%

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Unsupervised Network Analysis of the Plastic Supraoptic Nucleus Transcriptome Predicts Caprin2 Regulatory Interactions

Loh

Jahans-Price

Greenwood

et al. 2017

eNeuro

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The supraoptic nucleus (SON) is a group of neurons in the hypothalamus responsible for the synthesis and secretion of the peptide hormones vasopressin and oxytocin. Following physiological cues, such as dehydration, salt-loading and lactation, the SON undergoes a function related plasticity that we have previously described in the rat at the transcriptome level. Using the unsupervised graphical lasso (Glasso) algorithm, we reconstructed a putative network from 500 plastic SON genes in which genes are the nodes and the edges are the inferred interactions. The most active nodal gene identified within the network was Caprin2. Caprin2 encodes an RNA-binding protein that we have previously shown to be vital for the functioning of osmoregulatory neuroendocrine neurons in the SON of the rat hypothalamus. To test the validity of the Glasso network, we either overexpressed or knocked down Caprin2 transcripts in differentiated rat pheochromocytoma PC12 cells and showed that these manipulations had significant opposite effects on the levels of putative target mRNAs. These studies suggest that the predicative power of the Glasso algorithm within an in vivo system is accurate, and identifies biological targets that may be important to the functional plasticity of the SON.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Significance Testing Of Microarray Datamentioning

confidence: 99%

“…6 A ), or an Adenoviral vector expressing full-length rat Caprin2 cDNA (Konopacka et al, 2015) to elicit overexpression (Fig. 6 B ).…”

Section: Significance Testing Of Microarray Datamentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Unsupervised Network Analysis of the Plastic Supraoptic Nucleus Transcriptome Predicts Caprin2 Regulatory Interactions

Loh

Jahans-Price

Greenwood

et al. 2017

eNeuro

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Crystal structure of a 123 amino acids dimerization domain of Drosophila Caprin

et al. 2020

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Cytoplasmic activation/proliferation-associated protein (Caprin) proteins assume diverse functions in many important biological processes, including synaptic plasticity, stress response, innate immune response, and cellular proliferation. The Caprin family members are characterized by the presence of a highly conserved homologous region (HR1) at the N-terminus and arginine-glycine-rich (RGG) boxes at the C-terminus. We had previously determined the crystal structures of human Caprin-1 and Caprin-2 fragments corresponding to the C-terminal 2/3 of HR1. Both fragments adopt homodimeric structures. Based on sequence conservation, we speculated that all Caprin proteins should have similar homodimeric structures. Here we report the crystal structure of a fragment (residues 187-309) of Drosophila melanogaster Caprin (dCaprin). The dCaprin fragment adopts an all α-helical fold which self-associates to form a homodimer. The overall dCaprin homodimeric structure is similar to the Caprin-1 and Caprin-2 homodimeric structures. Most of the amino acids residues mediating homodimerization in the three structures are conserved among all Caprin family members. These structural and sequence data suggest that homodimerization through a conserved dimerization domain is a common structural feature of the Caprin protein family. The dimeric structures may also be involved in interaction with Caprin partners. Dimer formation creates a V-shape concave surface that may serve as a protein binding groove. The concave surfaces in Caprin-1, Caprin-2, and dCaprin should have different and specific binding partners due to the large difference in electrostatic potentials. We propose the existence of a multi-functional domain in Caprin proteins, which not only mediate homodimerization but also involve in interaction with specific Caprin partners.

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The effects of aging on biosynthetic processes in the rat hypothalamic osmoregulatory neuroendocrine system

Greenwood

Romanova

et al. 2018

Neurobiology of Aging

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Elderly people exhibit a diminished capacity to cope with osmotic challenges such as dehydration. We have undertaken a detailed molecular analysis of arginine vasopressin (AVP) biosynthetic processes in the supraoptic nucleus (SON) of the hypothalamus and secretory activity in the posterior pituitary of adult (3 months) and aged (18 months) rats, to provide a comprehensive analysis of age-associated changes to the AVP system. By matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, we identified differences in pituitary peptides, including AVP, in adult and aged rats under both basal and dehydrated states. In the SON, increased Avp gene transcription, coincided with reduced Avp promoter methylation in aged rats. Based on transcriptome data, we have previously characterized a number of novel dehydration-induced regulatory factors involved in the response of the SON to osmotic cues. We found that some of these increase in expression with age, while dehydration-induced expression of these genes in the SON was attenuated in aged rats. In summary, we show that aging alters the rat AVP system at the genome, transcriptome, and peptidome levels. These alterations however did not affect circulating levels of AVP in basal or dehydrated states.

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RNA binding protein Caprin-2 is a pivotal regulator of the central osmotic defense response

Cited by 17 publications

References 44 publications

Unsupervised Network Analysis of the Plastic Supraoptic Nucleus Transcriptome Predicts Caprin2 Regulatory Interactions

Unsupervised Network Analysis of the Plastic Supraoptic Nucleus Transcriptome Predicts Caprin2 Regulatory Interactions

Crystal structure of a 123 amino acids dimerization domain of Drosophila Caprin

The effects of aging on biosynthetic processes in the rat hypothalamic osmoregulatory neuroendocrine system

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