TY - JOUR
T1 - Nucleoporins NPP-1, NPP-3, NPP-4, NPP-11 and NPP-13 are required for proper spindle orientation in C. elegans
AU - Schetter, Aaron
AU - Askjaer, Peter
AU - Piano, Fabio
AU - Mattaj, Iain
AU - Kemphues, Kenneth
N1 - Funding Information:
We would like to thank Dr. Susan Strome for providing the PGL-1::GFP strain, Dr. Matthias Peter for providing the CSN-5 antibodies, Dr. Yuji Kohara for providing several ESTs, Dr. Donato Aceto for providing the PAR-6::GFP strain, Dr. Jun Kelly Liu for other necessary reagents and advice and the Caenorhabditis Genetics Center for providing various strains. We also thank Mona Hassab for providing technical assistance. This work was supported by NIH Institute of Child Health and Development Grant HD27698. A.S. was supported by a NIH training grant in Genetics and Development #6M07617. P.A. was supported by the Deutsche Forschungsgemeinschaft and EMBL. A.S. is currently supported by the Cancer Prevention Fellowship Program, Division of Cancer Prevention, National Cancer Institute.
PY - 2006/1/15
Y1 - 2006/1/15
N2 - Nucleoporins are components of the nuclear pore, which is required for nucleo-cytoplasmic transport. We report a role for a subclass of nucleoporins in orienting the mitotic spindle in C. elegans embryos. RNAi-mediated depletion of any of five putative nucleoporins npp-1, npp-3, npp-4, npp-11, and npp-13 leads to indistinguishable spindle orientation defects. Transgenic worms expressing NPP-1::GFP or NPP-11::GFP show GFP localization at the nuclear envelope, consistent with their predicted function. NPP-1 interacts with the other nucleoporins in yeast two-hybrid assays, suggesting that the proteins affect spindle orientation by a common process. The failed orientation phenotype of npp-1(RNAi) is at least partially epistatic to the ectopic spindle rotation in the AB blastomere of par-3 mutant embryos. This suggests that NPP-1 contributes to the mechanics of spindle orientation. However, NPP-1 is also required for PAR-6 asymmetry at the two-cell stage, indicating that nucleoporins may be required to define cortical domains in the germ line blastomere P1. Nuclear envelope structure is abnormal in npp-1(RNAi) embryos, but the envelope maintains its integrity, and most nuclear proteins we assayed accumulate normally. These findings raise the possibility that these nucleoporins may have direct roles in orienting the mitotic spindle and the maintenance of cell polarity.
AB - Nucleoporins are components of the nuclear pore, which is required for nucleo-cytoplasmic transport. We report a role for a subclass of nucleoporins in orienting the mitotic spindle in C. elegans embryos. RNAi-mediated depletion of any of five putative nucleoporins npp-1, npp-3, npp-4, npp-11, and npp-13 leads to indistinguishable spindle orientation defects. Transgenic worms expressing NPP-1::GFP or NPP-11::GFP show GFP localization at the nuclear envelope, consistent with their predicted function. NPP-1 interacts with the other nucleoporins in yeast two-hybrid assays, suggesting that the proteins affect spindle orientation by a common process. The failed orientation phenotype of npp-1(RNAi) is at least partially epistatic to the ectopic spindle rotation in the AB blastomere of par-3 mutant embryos. This suggests that NPP-1 contributes to the mechanics of spindle orientation. However, NPP-1 is also required for PAR-6 asymmetry at the two-cell stage, indicating that nucleoporins may be required to define cortical domains in the germ line blastomere P1. Nuclear envelope structure is abnormal in npp-1(RNAi) embryos, but the envelope maintains its integrity, and most nuclear proteins we assayed accumulate normally. These findings raise the possibility that these nucleoporins may have direct roles in orienting the mitotic spindle and the maintenance of cell polarity.
KW - Caenorhabditis elegans
KW - Embryo
KW - Nucleoporins
KW - Spindle orientation
UR - http://www.scopus.com/inward/record.url?scp=30044448679&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=30044448679&partnerID=8YFLogxK
U2 - 10.1016/j.ydbio.2005.10.038
DO - 10.1016/j.ydbio.2005.10.038
M3 - Article
C2 - 16325795
AN - SCOPUS:30044448679
SN - 0012-1606
VL - 289
SP - 360
EP - 371
JO - Developmental Biology
JF - Developmental Biology
IS - 2
ER -