Nuclear High Mobility Group A2 (HMGA2) Interactome Revealed by Biotin Proximity Labeling.

The non-histone chromatin binding protein High Mobility Group AT-hook protein 2 (HMGA2) has important functions in chromatin remodeling, and genome maintenance and protection. Expression of HMGA2 is highest in embryonic stem cells, declines during cell differentiation and cell aging, but it is re-expressed in some cancers, where high HMGA2 expression frequently coincides with a poor prognosis. The nuclear functions of HMGA2 cannot be explained by binding to chromatin alone but involve complex interactions with other proteins that are incompletely understood.

Functional comparison of human ACVR1 and zebrafish Acvr1l FOP-associated variants in embryonic zebrafish.

Background: Fibrodysplasia ossificans progressiva (FOP), a rare disease characterized by progressive heterotopic ossification of muscle and connective tissues, is caused by autosomal dominant activating mutations in the type I receptor, ACVR1/ALK2. The classic human FOP variant, ACVR1 , shows increased bone morphogenetic protein (BMP) signaling and activation by activins.

Results: Here, we performed in vivo functional characterization of human ACVR1 and orthologous zebrafish Acvr1l using early embryonic zebrafish dorsoventral patterning as a phenotypic readout for receptor activity.

The ribosomal RNA processing 1B:protein phosphatase 1 holoenzyme reveals non-canonical PP1 interaction motifs.

The serine/threonine protein phosphatase 1 (PP1) dephosphorylates hundreds of substrates by associating with >200 regulatory proteins to form specific holoenzymes. The major PP1 targeting protein in the nucleolus is RRP1B (ribosomal RNA processing 1B). In addition to selectively recruiting PP1β/PP1γ to the nucleolus, RRP1B also has a key role in ribosome biogenesis, among other functions.

A CRISPR/Cas9 zebrafish lamin A/C mutant model of muscular laminopathy.

Background: Lamin A/C gene (LMNA) mutations frequently cause cardiac and/or skeletal muscle diseases called striated muscle laminopathies. We created a zebrafish muscular laminopathy model using CRISPR/Cas9 technology to target the zebrafish lmna gene.

Results: Heterozygous and homozygous lmna mutants present skeletal muscle damage at 1 day post-fertilization (dpf), and mobility impairment at 4 to 7 dpf.

Protein Kinase C Alpha Cellular Distribution, Activity, and Proximity with Lamin A/C in Striated Muscle Laminopathies.

Striated muscle laminopathies are cardiac and skeletal muscle conditions caused by mutations in the lamin A/C gene (). codes for the A-type lamins, which are nuclear intermediate filaments that maintain the nuclear structure and nuclear processes such as gene expression. Protein kinase C alpha (PKC-α) interacts with lamin A/C and with several lamin A/C partners involved in striated muscle laminopathies.

Cellular and Animal Models of Striated Muscle Laminopathies.

The lamin A/C () gene codes for nuclear intermediate filaments constitutive of the nuclear lamina. has 12 exons and alternative splicing of exon 10 results in two major isoforms-lamins A and C. Mutations found throughout the gene cause a group of diseases collectively known as laminopathies, of which the type, diversity, penetrance and severity of phenotypes can vary from one individual to the other, even between individuals carrying the same mutation.

Lamin A/C mutations in dilated cardiomyopathy.

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure and heart transplant. Mutations in 60 genes have been associated with DCM. Approximately 6% of all DCM cases are caused by mutations in the lamin A/C gene (LMNA).