The NC1/endostatin domain of Caenorhabditis elegans type XVIII collagen affects cell migration and axon guidance.
Type XVIII collagen is a homotrimeric basement membrane molecule of unknown function, whose COOH-terminal NC1 domain contains endostatin (ES), a potent antiangiogenic agent. The Caenorhabditis elegans collagen XVIII homologue, cle-1, encodes three developmentally regulated protein isoforms expressed predominantly in neurons. The CLE-1 protein is found in low amounts in all basement membranes but accumulates at high levels in the nervous system. Deletion of the cle-1 NC1 domain results in viable fertile animals that display multiple cell migration and axon guidance defects. Particular defects can be rescued by ectopic expression of the NC1 domain, which is shown to be capable of forming trimers. In contrast, expression of monomeric ES does not rescue but dominantly causes cell and axon migration defects that phenocopy the NC1 deletion, suggesting that ES inhibits the promigratory activity of the NC1 domain. These results indicate that the cle-1 NC1/ES domain regulates cell and axon migrations in C. elegans.
Ackley
B D
BD
Department of Cell and Molecular Biology, Northwestern University Medical School, Chicago, Illinois 60611, USA.
Crew
J R
JR
Elamaa
H
H
Pihlajaniemi
T
T
Kuo
C J
CJ
Kramer
J M
JM
D000595:Amino Acid Sequence; D020533:Angiogenesis Inhibitors / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001369:Axons / Q000502:physiology*; D015153:Blotting, Western; D017173:Caenorhabditis elegans / Q000166:cytology / Q000235:genetics / Q000502:physiology*; D002465:Cell Movement; D003094:Collagen / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D043170:Collagen Type XVIII; D043169:Endostatins; D017930:Genes, Reporter / Q000235:genetics; D008297:Male; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D010446:Peptide Fragments / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms; D017434:Protein Structure, Tertiary; D012313:RNA / Q000037:antagonists & inhibitors; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D020533:Angiogenesis Inhibitors; D043170:Collagen Type XVIII; D043169:Endostatins; D010446:Peptide Fragments; D020033:Protein Isoforms; D011993:Recombinant Fusion Proteins; D012313:RNA; D003094:Collagen