Disease relevance of sls

• Mutations in SALL4, the human homolog of the Drosophila homeotic gene spalt (sal), cause the autosomal dominant disorder known as Okihiro syndrome [1].

High impact information on sls

• After extraction of the kettin-associated actin, the A-band edges were also stained [2].
• Kettin along with projectin may constitute the elastic filament system of insect IFM and determine the muscle's high stiffness necessary for stretch activation [2].
• Dotblot analysis revealed binding of COOH-terminal kettin domains to myosin [2].
• Immunoblotting demonstrated the presence of kettin isoforms in normal Drosophila IFM myofibrils and in myofibrils from an actin-null mutant [2].
• Micrographs of stretched IFM sarcomeres labeled with kettin antibodies revealed staining of the Z-disc periphery [2].

Biological context of sls

• D-Titin: a giant protein with dual roles in chromosomes and muscles [3].
• Mutations in D-Titin cause chromosome undercondensation, chromosome breakage, loss of diploidy, and premature sister chromatid separation [3].
• Phenotype assays on the allelic series of D-Titin mutants demonstrated that D-Titin plays an essential role in muscle development [4].
• Kettin appears to be the NH2-terminal one third of D-Titin, presumably expressed via alternative splicing [4].
• Here, we determined the entire nucleotide sequence of Drosophila melanogaster kettin, deduced the amino acid sequence of its protein product (540 kD) along with that of the Caenorhabditis elegans counterpart, and found that the overall primary structure of Kettin has been highly conserved in evolution [5].

Anatomical context of sls

• Calpain digests kettin to a series of peptides of between 30 and 170 kDa which are released from the myofibril [6].
• Additionally, D-Titin mutants have defects in myoblast fusion and muscle organization [3].
• Drosophila D-titin is required for myoblast fusion and skeletal muscle striation [4].
• First, D-Titin has an unsuspected function in myoblast fusion during myogenesis and, second, D-Titin later serves to organize myofilaments into the highly ordered arrays underlying skeletal muscle striation [4].
• Other muscles in the thorax and legs have longer Sls isoforms with varying amounts of PEVK sequence; all span the I-band to the ends of the thick filaments [7].

Associations of sls with chemical compounds

• D-Titin has 53 repeats of the immunoglobulin C2 domain, 6 repeats of the fibronectin type III domain and two large PEVK domains [4].

Regulatory relationships of sls

• Similarly, the 5' end of the Stretchin-Mlck transcription unit can also express transcripts encoding kettin and Unc-89-like isoforms, which share no sequences with the MLCK-like transcripts [8].

Other interactions of sls

• Digestion of kettin may cause disintegration of the Z-disc and alpha-actinin release which lead to disassembly of the myofibril [6].
• The 5' half of sls codes for zormin and kettin; both proteins contain Ig domains and can be expressed as separate isoforms, or as larger proteins linked to sequence downstream [7].
• Here we demonstrate that several MARs both specifically bind and contain multiple sites of cleavage by topoisomerase II, a major protein of the mitotic chromosomal scaffold [9].
• The genetics and molecular biology of the titin/connectin-like proteins of invertebrates [10].
• Antibody to insect kettin labelled the pharyngeal, body wall, anal depressor and proximal gonadal muscles in adult worms [11].

Analytical, diagnostic and therapeutic context of sls

• In line with the smaller length, immunoelectron microscopy locates the insect mini-titin to the I band and a very short portion of the A band only, while vertebrate titin is known to connect the Z band to the M band [12].
• Northern blot analysis showed that Bm Kettin mRNA was 9.1kb in length, and that the level of the mRNA in males was two times greater than that of females [13].
• Southern blot analysis revealed that Bm kettin was present at one copy in the genome [13].
• Fluorescent in situ hybridization with transposable element probes to mitotic chromosomal heterochromatin of Drosophila [14].

References