High impact information on unc-52

• Twelve mutants in the unc-52 II gene exhibit markedly retarded sarcomere construction and progressive paralysis [1].
• Several unc-52 mutants, such as the severely paralyzed SU200, produced only 2--3 sarcomeres per body-wall muscle cell, while the other mildly paralyzed unc-52 mutants, such as SU250, build 3--4 sarcomeres per muscle cell [1].
• The unc-52 body-wall sarcomeres become moderately disorganized as they are outstripped by cell growth; sufficient order is preserved, however, so that the majority of thick and thin filaments still interdigitate [1].
• The first domain is unique to the unc-52 polypeptide, whereas the three remaining domains contain sequences found in the LDL receptor (domain II) laminin (domain III) and N-CAM (domain IV) [2].
• Here, we demonstrate that the unc-52 gene encodes a nematode homolog of perlecan, the mammalian basement membrane heparan sulfate proteoglycan [2].

Biological context of unc-52

• We propose that smu-1 encodes a trans-acting factor that regulates the alternative splicing of the pre-mRNA of unc-52 and other genes [3].
• We show that a presumptive null mutation in smu-1 suppresses nonsense mutations in exon 17 but not exon 18 of unc-52 and enhances the phenotype conferred by an unc-52 splice site mutation in intron 16 [3].
• Mutations in the unc-52 gene responsible for body wall muscle defects in adult Caenorhabditis elegans are located in alternatively spliced exons [4].
• Previous work has shown that C. elegans MEC-8 is a putative RNA-binding protein that promotes specific alternative splices of unc-52 transcripts. unc-52 encodes homologs of mammalian perlecan that are located extracellularly between muscle and hypodermis and are essential for muscle development in both embryos and larvae [5].
• The unc-52 gene plays an essential role in myofilament assembly in body-wall muscle during embryonic development [6].

Anatomical context of unc-52

• Mutations in the unc-52 gene of Caenorhabditis elegans affect attachment of the myofilament lattice to the muscle cell membrane [2].
• The effects of unc-52 mutations on DTC migrations are distinct from effects on myofilament organization and can be partially suppressed by mutations in several genes encoding growth factor-like molecules, including EGL-17/FGF, UNC-129/TGF-beta, DBL-1/TGF-beta, and EGL-20/WNT [7].
• We have also found that overexpression of MEC-8 in hypodermis but not muscle can suppress certain unc-52 mutant phenotypes [5].
• The unc-52 gene encodes the nematode homologue of mammalian perlecan, the major heparan sulfate proteoglycan of the extracellular matrix [8].

Regulatory relationships of unc-52

• We have used reverse transcription-PCR and RNase protection experiments to show that mec-8 regulates the accumulation of a specific subset of alternatively spliced unc-52 transcripts [9].

Other interactions of unc-52

• Analysis of smu-1, a gene that regulates the alternative splicing of unc-52 pre-mRNA in Caenorhabditis elegans [3].
• Mutations in the Caenorhabditis elegans gene smu-2 suppress mec-8 and unc-52 mutations [10].
• In strains which are chronically starved as a result of mutations which compromise feeding behaviour (unc-52) or nutrient uptake into the intestinal cells (daf-4), cathepsin D levels are decreased to about 15% of the level in fully fed wild-type animals [11].
• The suppression pattern of the suppressor against the two muscle-affecting genes, unc-15 and unc-52, suggested that either the suppressors are expressed in a developmental stage-specific manner or that the unc-52 products are expressed in cell-types other than muscle, possibly hypodermis [12].

References