title: C. elegans dysferlin homolog fer-1 is expressed in muscle, and fer-1 mutations initiate altered gene expression of muscle enriched genes.
abstract: Mutations in the human dysferlin gene cause Limb Girdle Muscular Dystrophy 2B (LGMD2B). The Caenorhabditis elegans dysferlin homolog, fer-1, affects sperms development but is not known to be expressed in or have a functional roles outside of the male germline. Using several approaches, we show that fer-1 mRNA is present in C. elegans muscle cells but is absent from neurons. In mammals, loss of muscle-expressed dysferlin causes transcriptional deregulation of muscle expressed genes. To determine if similar alterations in gene expression are initiated in C. elegans due to loss of muscle-expressed fer-1, we performed whole genome Affymetrix microarray analysis of two loss-of-function fer-1 mutants. Both mutants gave rise to highly similar changes in gene expression and altered the expression of 337 genes. Using multiple analysis methods, we show that this gene set is enriched for genes known to regulate the structure and function of muscle. However, these transcriptional changes do not appear to be in response to gross sarcomeric damage, since genetically sensitized fer-1 mutants exhibit normal thin filament organization. Our data suggest that processes other than sarcomere stability may be affected by loss of fer-1 in C. elegans muscle. Therefore, C. elegans may be an attractive model system in which to explore new muscle-specific functions of the dysferlin protein and gain insights into the molecular pathogenesis of LGMD2B.
authors.affiliation: Department of Physiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
authors.forename: Predrag
authors.initials: P
authors.lastname: Krajacic
authors.forename: Jane
authors.initials: J
authors.lastname: Hermanowski
authors.forename: Olga
authors.initials: O
authors.lastname: Lozynska
authors.forename: Tejvir S
authors.initials: TS
authors.lastname: Khurana
authors.forename: Todd
authors.initials: T
authors.lastname: Lamitina
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D002478:Cells, Cultured; D016000:Cluster Analysis; D000073939:Dysferlin; D005786:Gene Expression Regulation; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism; D032342:Muscle Cells / Q000378:metabolism; D009124:Muscle Proteins / Q000737:chemistry*; D009132:Muscles / Q000166:cytology / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D009928:Organ Specificity / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015203:Reproducibility of Results; D017386:Sequence Homology, Amino Acid; D014158:Transcription, Genetic
chemical_list: D029742:Caenorhabditis elegans Proteins; C114839:DYSF protein, human; D000073939:Dysferlin; C106933:FER-1 protein, C elegans; D008565:Membrane Proteins; D009124:Muscle Proteins; D012333:RNA, Messenger