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PMID:21130760

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Citation

Hetherington, S, Gally, C, Fritz, JA, Polanowska, J, Reboul, J, Schwab, Y, Zahreddine, H, Behm, C and Labouesse, M (2011) PAT-12, a potential anti-nematode target, is a new spectraplakin partner essential for Caenorhabditis elegans hemidesmosome integrity and embryonic morphogenesis. Dev. Biol. 350:267-78

Abstract

Caenorhabditis elegans embryonic elongation depends on both epidermal and muscle cells. The hemidesmosome-like junctions, commonly called fibrous organelles (FOs), that attach the epidermis to the extracellular matrix ensure muscle anchoring to the cuticular exoskeleton and play an essential role during elongation. To further define how hemidesmosomes might control elongation, we searched for factors interacting with the core hemidesmosome component, the spectraplakin homolog VAB-10. Using the VAB-10 plakin domain as bait in a yeast two-hybrid screen, we identified the novel protein T17H7.4. We also identified T17H7.4 in an independent bioinformatic search for essential nematode-specific proteins that could define novel anti-nematode drug or vaccine targets. Interestingly, T17H7.4 corresponds to the C. elegans equivalent of the parasitic OvB20 antigen, and has a characteristic hemidesmosome distribution. We identified two mutations in T17H7.4, one of which defines the uncharacterized gene pat-12, previously identified in screens for genes required for muscle assembly. Using isoform-specific GFP constructs, we showed that one pat-12 isoform with a hemidesmosome distribution can rescue a pat-12 null allele. We further found that lack of pat-12 affects hemidesmosome integrity, with marked defects at the apical membrane. PAT-12 defines a novel component of C. elegans hemidesmosomes, which is required for maintaining their integrity. We suggest that PAT-12 helps maintaining VAB-10 attachment with matrix receptors.

Links

PubMed Online version:10.1016/j.ydbio.2010.11.025

Keywords

Animals; Antinematodal Agents; Biogenesis; Caenorhabditis elegans/drug effects; Caenorhabditis elegans/embryology; Caenorhabditis elegans Proteins/antagonists & inhibitors; Caenorhabditis elegans Proteins/genetics; Caenorhabditis elegans Proteins/physiology; HeLa Cells; Hemidesmosomes/physiology; Humans; Morphogenesis; Organelles/physiology

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

CAEEL:G5EDD3

enables

GO:0005515: protein binding

ECO:0000353: physical interaction evidence used in manual assertion

UniProtKB:Q95QA6

F

Seeded From UniProt

complete

CAEEL:PAT12

involved_in

GO:0031581: hemidesmosome assembly

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00251200

P

Seeded From UniProt

complete

CAEEL:PAT12

located_in

GO:0030056: hemidesmosome

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

CAEEL:PAT12

involved_in

GO:0048598: embryonic morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

WB:WBVar00251200

P

Seeded From UniProt

complete


See also

References

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