TY - JOUR
T1 - Connections between integrins and Rac GTPase pathways control gonad formation and function in C. elegans
AU - Lee, Myeongwoo
AU - Shen, Bing
AU - Schwarzbauer, Jean E.
AU - Ahn, Jeong
AU - Kwon, John
N1 - Funding Information:
The C. elegans mutant strains used in this study were provided by the Caenorhabditis Genetics Center, St. Paul, MN, USA, which is funded by NIH. We thank Erin Cram, Kevin Gutzwiller, and Jose Guardiola for advice on statistical analysis. We are grateful to Hyun Jun Park for his assistance, and Anthony Otsuka, Erin Cram, Christopher Meighan, Jeff Thomas, and Kyuhyung Kim for critical reading of this manuscript.
PY - 2005/5/25
Y1 - 2005/5/25
N2 - The integrins are a family of αβ heterodimeric transmembrane receptors that link extracellular matrix (ECM) proteins to the cytoskeleton and orchestrate cell behaviors. It's been suggested that integrins interact with Rho family small GTPases, such as Rho and Rac. We took advantage of a C. elegans nematode line expressing HA-βtail, a β integrin transgene inhibiting the functions of endogenous integrins, to determine the combined effects of reducing PAT-3 β integrin and Rac pathway activities. Double mutants of HA-βtail and unc-73, a guanine nucleotide exchange factor GEF for MIG-2/Rac, had body wall and vulval muscle abnormalities. On the other hand, HA-βtail combined with mutant CED-5, another Rac interacting protein, showed ovulation defects and sterility. RNA-mediated interference (RNAi) of pat-3 on Rac mutant backgrounds also affected gonad structure and function. These results show a functional link between integrins and Rac signaling in muscles and gonads. Furthermore, data showing distinct phenotypes of HA-βtail with unc-73 versus ced-5 suggest some tissue-specificity in the usage of Rac signaling pathways.
AB - The integrins are a family of αβ heterodimeric transmembrane receptors that link extracellular matrix (ECM) proteins to the cytoskeleton and orchestrate cell behaviors. It's been suggested that integrins interact with Rho family small GTPases, such as Rho and Rac. We took advantage of a C. elegans nematode line expressing HA-βtail, a β integrin transgene inhibiting the functions of endogenous integrins, to determine the combined effects of reducing PAT-3 β integrin and Rac pathway activities. Double mutants of HA-βtail and unc-73, a guanine nucleotide exchange factor GEF for MIG-2/Rac, had body wall and vulval muscle abnormalities. On the other hand, HA-βtail combined with mutant CED-5, another Rac interacting protein, showed ovulation defects and sterility. RNA-mediated interference (RNAi) of pat-3 on Rac mutant backgrounds also affected gonad structure and function. These results show a functional link between integrins and Rac signaling in muscles and gonads. Furthermore, data showing distinct phenotypes of HA-βtail with unc-73 versus ced-5 suggest some tissue-specificity in the usage of Rac signaling pathways.
KW - Cell migration
KW - Fertility
KW - Gonad
KW - Integrin
KW - Muscle
KW - Rac GTPase
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U2 - 10.1016/j.bbagen.2005.01.003
DO - 10.1016/j.bbagen.2005.01.003
M3 - Article
C2 - 15716039
AN - SCOPUS:19744373239
SN - 0304-4165
VL - 1723
SP - 248
EP - 255
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 1-3
ER -