UniProt release 2015_09
Published September 16, 2015
Life (and death) in 2D
While the cinema industry struggles to produce ever more realistic 3D, even 4D, films out of 2D images, scientists have achieved the exact opposite: in a collection of (3D) vertebrate embryos, they have identified a mutant that flattens in the course of development.
Vertebrates have a defined body shape in which correct tissue and organ shape and alignment are essential for function. Correct morphogenesis depends on force generation, force transmission through the tissue, and the response of tissues and extracellular matrix to force. In addition, embryos must be able to withstand environmental perturbations, such as gravity. Already in 1917, in his master work “On Growth and Form”, Sir D’Arcy Wentworth Thompson postulated that “the forms as well the actions of our bodies are entirely conditioned (save for certain exceptions in the case of aquatic animals) by the strength of gravity upon this globe”. It is actually from an “aquatic animal”, a fish, that the confirmation of this hypothesis came earlier this year. Screening of a Japanese rice fish mutant identified an embryo that displayed pronounced body flattening around stage 25-28 (50-64 h post fertilization). Although general development was not delayed, the mutant exhibited delayed blastopore closure and progressive body collapse from mid-neurulation, surviving until just before hatching. This mutant was aptly named hirame, which means flatfish in Japanese. When embryos were grown in agarose, their collapse correlated with the direction of gravity, reflecting the mutant’s inability to withstand external forces. The mutants also showed defective fibronectin fibril formation.
The hirame mutation lies within the Yap1 gene and creates a premature stop codon at position 164. Yap1 is a transcriptional co-activator that promotes proliferation and inhibits cell death during embryonic development. Porazinski and colleagues showed that Yap1 is also essential for actomyosin-mediated tissue tension.
The hypothesis with the strongest experimental support is that YAP1 acts on ARHGAP18 expression (and possibly that of other ARHGAP18-related genes), which in turn regulates cortical actomyosin network formation. Actomyosin contraction promotes fibronectin assembly, which could be a critical in vivo mechanism for the integration of mechanical signals, such as tension generated by actomyosin, with biochemical signals, such as integrin signaling, ensuring proper tissue shape and alignment and appropriate organ and body shape.
YAP1 knockdown in the human cell line hTERT-RPE1 caused a phenotype reminiscent of the fish embryo phenotype. When cultured in a 3D spheroid system, these retinal epithelial cells also exhibited collapse upon exposure to external forces, marked reduction of cortical F-actin bundles and lack of typical fibronectin fibril pattern. This suggests that YAP1 orthologs may play a similar role in all vertebrates, and possibly beyond.
As of this release, YAP1 protein entries have been updated and are publicly available.
Release of variation files for 27 new species
In collaboration with Ensembl and Ensembl Genomes, UniProt would like to announce the release of variation files for 27 species in addition to human, mouse and zebrafish files currently available in the dedicated variants directory on the UniProt FTP sites. This release includes a further 13 vertebrate species, including agriculturally important species: cow, chicken, pig and sheep. These new variant catalogues also expand the diversity of species with variants for plant, fungi and protist species that includes rice, bread wheat, barley and grape.
Changes to the controlled vocabulary of human diseases
- Brugada syndrome 9
- Cardiomyopathy, familial hypertrophic 23, with or without left ventricular non-compaction
- CHOPS syndrome
- Ciliary dyskinesia, primary, 31
- Dystonia 2, torsion, autosomal recessive
- Lactate dehydrogenase B deficiency
- Mandibulofacial dysostosis with alopecia
- Mental retardation, autosomal dominant 38
- Microcephaly 14, primary, autosomal recessive
- Mitochondrial myopathy with lactic acidosis
- Multiple mitochondrial dysfunctions syndrome 4
- Night blindness, congenital stationary, 1G
- Palmoplantar keratoderma, non-epidermolytic, focal 2
- Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 3
- Pulmonary fibrosis, and/or bone marrow failure, telomere-related, 4
- Retinal dystrophy, early-onset, with or without pituitary dysfunction
- Retinitis pigmentosa 71
- Tortuosity of retinal arteries
- Trichothiodystrophy 2, photosensitive
- Trichothiodystrophy 3, photosensitive
- Trichothiodystrophy 5, non-photosensitive
- Aplasia cutis congenita, reticulolinear, with microcephaly, facial dysmorphism and other congenital anomalies -> Linear skin defects with multiple congenital anomalies 2
- Cardiomyopathy, dilated 1AA -> Cardiomyopathy, dilated 1AA, with or without left ventricular non-compaction
- Cardiomyopathy, dilated 1N -> Cardiomyopathy, familial hypertrophic 25””:/diseases/DI-00220
- Immunodeficiency 38 -> Immunodeficiency 38, with basal ganglia calcification
- Inclusion body myopathy 3 -> Myopathy, proximal, and ophthalmoplegia
- Intestinal atresia, multiple -> Gastrointestinal defects and immunodeficiency syndrome
- Mental retardation, autosomal dominant 28 -> Helsmoortel-van der Aa syndrome
- Microphthalmia, syndromic, 7 -> Linear skin defects with multiple congenital anomalies 1
- Night blindness, congenital stationary, 2B -> Cone-rod synaptic disorder, congenital non-progressive
- Prader-Willi-like syndrome -> Schaaf-Yang syndrome
- Succinyl-CoA-3-ketoacid-CoA transferase deficiency -> Succinyl-CoA:3-oxoacid CoA transferase deficiency
- Trichothiodystrophy photosensitive -> Trichothiodystrophy 1, photosensitive
- Trichothiodystrophy non-photosensitive 1 -> Trichothiodystrophy 4, non-photosensitive
- Trifunctional protein deficiency -> Mitochondrial trifunctional protein deficiency