Suppression of mig-17 DTC migration defects by a dominant mutation in mig-22 Export

@inproceedings{citeulike:3337304, abstract = {"The U-shape of the gonad arms is formed by directional movement of distal tip cells (DTCs), which is regulated by MIG-17, an ADAMTS protease. To obtain further insights into the molecular mechanisms of DTC migration involving MIG-17, we isolated suppressor mutants of mig-17 DTC migration defects. One of these, k185 was a dominant suppressor and we identified a missense mutation in the mig-22 gene on LGIII. We previously reported that the MIG-22 protein is chondroitin polymerizing factor, a co-factor for chondroitin synthase whose loss-of-function mutations(k141 and tk24) cause abnormal DTC migration similar to that seen in mig-17 mutants (Suzuki et al., Dev. Biol. 300: 635, 2006). Double mutants between mig-17(null) and mig-22 alleles showed enhanced DTC migration defects, suggesting that these genes do not constitute a single pathway. Because mig-22(k185) mutant showed normal DTC migration, k185 does not appear to be a simple loss-of-function mutation. The suppression activity was strongest in k185/185, moderate in k185/+, weak in k185/0 and no activity in +/+, indicating that k185, is a gain-of-function mutation. A mutation in mig-22(k185) does not affect the amount of chondroitin or the levels of MIG-22 proteins. The expression of the mig-22(k185) gene under the control of the mig-24 promoter, which drives gene expressed in DTCs, rescued DTC migration defects of mig-17 mutants. Transgenic expression of the wild-type mig-22 under either a DTC or a seam cell-specific promoter also rescued mig-17. The expression of sqv-5, a gene for chondroitin synthase, under the mig-22 promoter failed to rescue mig-17. Surprisingly, however, abnormal DTC migration in sqv-5 (null) was rescued by mig-22(k185). In sqv-5(null);mig-17(null) animals, mig-22(k185) could not rescue the abnormal DTC migration, suggesting that the rescuing activity of mig-22(k185) for mig-17(null) depends on the function of SQV-5. We are examining whether specific chondroitin proteoglycans are involved in mig-22(k185) dependent-suppression of mig-17 by RNAi knockdown of core protein genes cpg1-9 reported by Olson et al., JCB 173: 985, 2006."}, author = {Sassa, Toshihiro and Toyoda, Hidenao and Ohkura, Kiyotaka and Nishiwaki, Kiyoji}, citeulike-article-id = {3337304}, citeulike-linkout-0 = {http://www.wormbase.org/db/misc/paper?name=WBPaper00031795}, keywords = {c28c128, c\_elegans, caenorhabditis\_elegans, celegans, elegans, f57b74, hlh-12, meeting\_abstract, mig-17, mig-22, nematode, par24, sqv-5, t24d11, wormbase}, posted-at = {2008-09-25 17:25:25}, priority = {3}, title = {Suppression of mig-17 DTC migration defects by a dominant mutation in mig-22}, url = {http://www.wormbase.org/db/misc/paper?name=WBPaper00031795} }

TY - CONF ID - citeulike:3337304 L3 - citeulike-article-id:3337304 N2 - "The U-shape of the gonad arms is formed by directional movement of distal tip cells (DTCs), which is regulated by MIG-17, an ADAMTS protease. To obtain further insights into the molecular mechanisms of DTC migration involving MIG-17, we isolated suppressor mutants of mig-17 DTC migration defects. One of these, k185 was a dominant suppressor and we identified a missense mutation in the mig-22 gene on LGIII. We previously reported that the MIG-22 protein is chondroitin polymerizing factor, a co-factor for chondroitin synthase whose loss-of-function mutations(k141 and tk24) cause abnormal DTC migration similar to that seen in mig-17 mutants (Suzuki et al., Dev. Biol. 300: 635, 2006). Double mutants between mig-17(null) and mig-22 alleles showed enhanced DTC migration defects, suggesting that these genes do not constitute a single pathway. Because mig-22(k185) mutant showed normal DTC migration, k185 does not appear to be a simple loss-of-function mutation. The suppression activity was strongest in k185/185, moderate in k185/+, weak in k185/0 and no activity in +/+, indicating that k185, is a gain-of-function mutation. A mutation in mig-22(k185) does not affect the amount of chondroitin or the levels of MIG-22 proteins. The expression of the mig-22(k185) gene under the control of the mig-24 promoter, which drives gene expressed in DTCs, rescued DTC migration defects of mig-17 mutants. Transgenic expression of the wild-type mig-22 under either a DTC or a seam cell-specific promoter also rescued mig-17. The expression of sqv-5, a gene for chondroitin synthase, under the mig-22 promoter failed to rescue mig-17. Surprisingly, however, abnormal DTC migration in sqv-5 (null) was rescued by mig-22(k185). In sqv-5(null);mig-17(null) animals, mig-22(k185) could not rescue the abnormal DTC migration, suggesting that the rescuing activity of mig-22(k185) for mig-17(null) depends on the function of SQV-5. We are examining whether specific chondroitin proteoglycans are involved in mig-22(k185) dependent-suppression of mig-17 by RNAi knockdown of core protein genes cpg1-9 reported by Olson et al., JCB 173: 985, 2006." TI - Suppression of mig-17 DTC migration defects by a dominant mutation in mig-22 KW - c28c128 KW - c_elegans KW - caenorhabditis_elegans KW - celegans KW - elegans KW - f57b74 KW - hlh-12 KW - meeting_abstract KW - mig-17 KW - mig-22 KW - nematode KW - par24 KW - sqv-5 KW - t24d11 KW - wormbase AU - Sassa, Toshihiro AU - Toyoda, Hidenao AU - Ohkura, Kiyotaka AU - Nishiwaki, Kiyoji UR - http://www.wormbase.org/db/misc/paper?name=WBPaper00031795 ER -