C. elegans ADAMTS ADT-2 regulates body size by modulating TGFβ signaling and cuticle collagen organization.
Organismal growth and body size are influenced by both genetic and environmental factors. We have utilized the strong molecular genetic techniques available in the nematode Caenorhabditis elegans to identify genetic determinants of body size. In C. elegans, DBL-1, a member of the conserved family of secreted growth factors known as the Transforming Growth Factor β superfamily, is known to play a major role in growth control. The mechanisms by which other determinants of body size function, however, is less well understood. To identify additional genes involved in body size regulation, a genetic screen for small mutants was previously performed. One of the genes identified in that screen was sma-21. We now demonstrate that sma-21 encodes ADT-2, a member of the ADAMTS (a disintegrin and metalloprotease with thrombospondin motifs) family of secreted metalloproteases. ADAMTS proteins are believed to remodel the extracellular matrix and may modulate the activity of extracellular signals. Genetic interactions suggest that ADT-2 acts in parallel with or in multiple size regulatory pathways. We demonstrate that ADT-2 is required for normal levels of expression of a DBL-1-responsive transcriptional reporter. We further demonstrate that adt-2 regulatory sequences drive expression in glial-like and vulval cells, and that ADT-2 activity is required for normal cuticle collagen fibril organization. We therefore propose that ADT-2 regulates body size both by modulating TGFβ signaling activity and by maintaining normal cuticle structure.
Department of Biology, Queens College, and The Graduate School and University Center, City University of New York, Flushing, NY 11367, USA.
Thilini
T
Fernando
Stephane
S
Flibotte
Sheng
S
Xiong
Jianghua
J
Yin
Edlira
E
Yzeiraj
Donald G
DG
Moerman
Alicia
A
Meléndez
Cathy
C
Savage-Dunn
D051722:ADAM Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D049628:Body Size; D017173:Caenorhabditis elegans / Q000033:anatomy & histology* / Q000166:cytology / Q000201:enzymology* / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D003094:Collagen / Q000378:metabolism*; D004843:Epistasis, Genetic; D017238:Genes, Helminth / Q000235:genetics; D017930:Genes, Reporter / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000378:metabolism; D034582:Integumentary System / Q000033:anatomy & histology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009479:Neuropeptides / Q000378:metabolism*; D010641:Phenotype; D034622:RNA Interference; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D016212:Transforming Growth Factor beta / Q000378:metabolism*
D029742:Caenorhabditis elegans Proteins; C117509:Dbl-1 protein, C elegans; D009479:Neuropeptides; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D049452:Green Fluorescent Proteins; D003094:Collagen; D051722:ADAM Proteins; C557993:ADT-2 protein, C elegans
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