Cloning, genomic organization and expression pattern of a novel Drosophila gene, the disco-interacting protein 2 ( dip2 ), and its murine homolog

Mukhopadhyay, Mahua; Pelka, Peter; Desousa, Dorothy; Kablar, Boris; Schindler, Alice B.; Rudnicki, Michael A.; Campos, Ana Regina Nascimento

doi:10.1016/s0378-1119(02)00694-7

Cited by 40 publications

(52 citation statements)

References 16 publications

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“…By motif analysis, CPS1 in C. heterostrophus was shown to belong to the AMP-binding superfamily and phylogenetic analysis initially suggested it could be part of a nonribosomal peptide synthase (NRPS) (7), but further evidence suggests it groups outside most NRPSs (26). CPS1 is part of the adenylate forming domain superfamily of proteins that includes the disco- interacting proteins (Dip2), such as DIP2 of Drosophila and Dip2A in mice and humans (27)(28)(29). Dip2A is a membrane receptor protein that binds secreted follistatin-like proteins which appear to regulate downstream gene expression.…”

Section: Discussionmentioning

confidence: 99%

A Coccidioides posadasii CPS1 Deletion Mutant Is Avirulent and Protects Mice from Lethal Infection

et al. 2016

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The CPS1 gene was identified as a virulence factor in the maize pathogen Cochliobolus heterostrophus. Hypothesizing that the homologous gene in Coccidioides posadasii could be important for virulence, we created a ⌬cps1 deletion mutant which was unable to cause disease in three strains of mice (C57BL/6, BALB/c, or the severely immunodeficient NOD-scid,␥c null [NSG]). Only a single colony was recovered from 1 of 60 C57BL/6 mice following intranasal infections of up to 4,400 spores. Following administration of very high doses (10,000 to 2.5 ؋ 10 7 spores) to NSG and BALB/c mice, spherules were observed in lung sections at time points from day 3 to day 10 postinfection, but nearly all appeared degraded with infrequent endosporulation. Although the role of CPS1 in virulence is not understood, phenotypic alterations and transcription differences of at least 33 genes in the ⌬cps1 strain versus C. posadasii is consistent with both metabolic and regulatory functions for the gene. The in vitro phenotype of the ⌬cps1 strain showed slower growth of mycelia with delayed and lower spore production than C. posadasii, and in vitro spherules were smaller. Vaccination of C57BL/6 or BALB/c mice with live ⌬cps1 spores either intranasally, intraperitoneally, or subcutaneously resulted in over 95% survival with mean residual lung fungal burdens of <1,000 CFU from an otherwise lethal C. posadasii intranasal infection. Considering its apparently complete attenuation of virulence and the high degree of resistance to C. posadasii infection when used as a vaccine, the ⌬cps1 strain is a promising vaccine candidate for preventing coccidioidomycosis in humans or other animals. Coccidioides species (C. immitis and C. posadasii) are the causative agents of coccidioidomycosis (valley fever), an important emerging disease endemic to the southwestern United States and elsewhere in the Western Hemisphere (1-3). Inhalation of a 2-to 4-m arthroconidium (spore) initiates a respiratory infection and grows as a unique parasitic phase structure, the spherule, to 80 to 100 m in diameter (4). During spherule maturation, which in mice takes approximately 4 days, internal cell division and septation results in hundreds of endospores that, if released, can reinitiate spherule growth in the infected tissue. Although many infections resolve without medical intervention, about 40% of infections cause respiratory illnesses that often last weeks to many months (5). In a small percentage of patients, infection disseminates from the lungs hematogenously to produce progressive, protracted, and even fatal complications. With or without clinical illness, most infections produce lifelong immunity to a second coccidioidal infection, and it is this observation that suggests a preventative vaccine could be developed (6).Interest in CPS1 came first from a search for general virulence factors in the maize pathogen Cochliobolus heterostrophus. In this and other ascomycete cereal grain pathogens, deletion of the CPS1 gene results in reduced virulence on host plants with prod...

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Section: Discussionmentioning

confidence: 99%

A Coccidioides posadasii CPS1 Deletion Mutant Is Avirulent and Protects Mice from Lethal Infection

et al. 2016

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“…Therefore, DIP2A can mediate multiple aspects of the cardiovascular protective actions attributed to FSTL1. DIP2 was initially identified by a yeast two-hybrid screen as a protein that interacts with a transcription factor encoded by the Drosophila Disco gene (22). Mutations in the Disco locus give rise to flies that exhibit abnormal neuronal connections in the visual system (23).…”

Section: Discussionmentioning

confidence: 99%

“…No functional studies have been performed on the Drosophila DIP2 protein or on its vertebrate homolog DIP2A. Analysis of Dip2 transcripts by in situ hybridization showed that the expression of this gene is observed in the nervous systems of Drosophila, and the mouse homolog is reported to be selectively expressed in the nervous system of the murine embryo (22). In contrast, in adult human tissues, the DIP2A transcript (also referred to as KIAA0184) is ubiquitously expressed (24).…”

Section: Discussionmentioning

confidence: 99%

DIP2A Functions as a FSTL1 Receptor

Ouchi

Asaumi

Ohashi

et al. 2010

Journal of Biological Chemistry

114

107

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FSTL1 is an extracellular glycoprotein whose functional significance in physiological and pathological processes is incompletely understood. Recently, we have shown that FSTL1 acts as a muscle-derived secreted factor that is up-regulated by Akt activation and ischemic stress and that FSTL1 exerts favorable actions on the heart and vasculature. Here, we sought to identify the receptor that mediates the cellular actions of FSTL1. We identified DIP2A as a novel FSTL1-binding partner from the membrane fraction of endothelial cells. Co-immunoprecipitation assays revealed a direct physical interaction between FSTL1 and DIP2A. DIP2A was present on the cell surface of endothelial cells, and knockdown of DIP2A by small interfering RNA reduced the binding of FSTL1 to cells. In cultured endothelial cells, knockdown of DIP2A by small interfering RNA diminished FSTL1-stimulated survival, migration, and differentiation into network structures and inhibited FSTL1-induced Akt phosphorylation. In cultured cardiac myocytes, ablation of DIP2A reduced the protective actions of FSTL1 on hypoxia/ reoxygenation-induced apoptosis and suppressed FSTL1-induced Akt phosphorylation. These data indicate that DIP2A functions as a novel receptor that mediates the cardiovascular protective effects of FSTL1.FSTL1 (follistatin-like 1; also referred to TSC36) is a secreted extracellular glycoprotein that was initially identified from a mouse osteoblast cell line as a transforming growth factor-␤ (TGF-␤) 2 -regulated gene (1). Prior studies have shown that FSTL1 can have antiproliferative effects on cells (2, 3) and that it can exert anti-inflammatory (4, 5) or pro-inflammatory (6) actions in animal models. Recently, we have found that FSTL1 is up-regulated in the myocardium in response to Akt1-induced hypertrophic growth and myocardial stress, including pressure overload, ischemia-reperfusion, and myocardial infarction (7). Systemic delivery of FSTL1 protects the heart from ischemiareperfusion injury in mice, which is accompanied by reduced myocyte apoptosis. More recently, we have shown that FSTL1 is up-regulated and secreted in skeletal muscle in response to Akt-mediated growth and ischemic injury (8). FSTL1 promotes endothelial cell function in vitro and accelerates ischemia-induced revascularization in vivo. Thus, we proposed that FSTL1 functions as an injury-induced secreted protein that protects against ischemic damage. However, the molecular mechanisms by which FSTL1 promotes cardiovascular cell protection and function are incompletely understood.FSTL1 possesses extracellular calcium-binding and follistatin-like domains and is categorized as the follistatin family member of proteins (9). Other members of the follistatin family act through their ability to function as extracellular binding partners of TGF-␤ superfamily proteins and antagonize the binding of these ligands to the receptors (10). However, it has never been documented that FSTL1 modulates cell function by binding members of the TGF-␤ superfamily, as do follistatin and FSTL3 (11...

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“…However, this inference of DIP2As function is incorrect as the authors have inadvertently identified DIP2A as ''DLX interacting protein 2 (DIP2)'' which is an alternatively spliced form of glutamate receptor interacting protein 1 (GRIP1 [MIM 604597]) [211], rather than ''DIP2 disco-interacting protein 2 homolog A (Drosophila)''. DIP2A may still be involved in neuronal connectivity although as shown by mutation experiments of the disconnected gene (disco) in Drosophila [125,180]. S100B is also an attractive candidate for DD susceptibility as SNPs within this gene have been associated with low cognitive ability in the elderly [100], schizophrenia [107] and bipolar disorder [149].…”

Section: Dyx8 On Chromosomementioning

confidence: 99%

“…In particular, DYX1C1, DCDC2, KIAA0319, S100B and ROBO1 have all been implicated in neuronal migration [20,121,135,150,189,198,199]. ROBO1 and DIP2A may also be involved in axon guidance and neural development [97,125,180]. This adds further weight to their involvement in DD because disruptions of these genes could result in the abnormalities observed from the postmortem examinations of DD brains, such as the focal architectonic dysplasias and neuronal ectopias which result from disruptions in neuronal migration [61,63,92].…”

Section: Dyx8 On Chromosomementioning

confidence: 99%

Genetics of developmental dyslexia

Scerri

Schulte‐Körne

2009

Eur Child Adolesc Psychiatry

191

137

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Developmental dyslexia is a highly heritable disorder with a prevalence of at least 5% in school-aged children. Linkage studies have identified numerous loci throughout the genome that are likely to harbour candidate dyslexia susceptibility genes. Association studies and the refinement of chromosomal translocation break points in individuals with dyslexia have resulted in the discovery of candidate genes at some of these loci. A key function of many of these genes is their involvement in neuronal migration. This complements anatomical abnormalities discovered in dyslexic brains, such as ectopias, that may be the result of irregular neuronal migration.

show abstract

Cloning, genomic organization and expression pattern of a novel Drosophila gene, the disco-interacting protein 2 ( dip2 ), and its murine homolog

Cited by 40 publications

References 16 publications

A Coccidioides posadasii CPS1 Deletion Mutant Is Avirulent and Protects Mice from Lethal Infection

A Coccidioides posadasii CPS1 Deletion Mutant Is Avirulent and Protects Mice from Lethal Infection

DIP2A Functions as a FSTL1 Receptor

Genetics of developmental dyslexia

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