The O-fucosyltransferase POFUT2 modulates the migration of the distal tip cell in C. elegans. Export

@inproceedings{citeulike:3333777, abstract = { Glycosyl-transferases add glycans to proteins that vary in structure from simple sugar chains to very complex ones. These modifications can drastically change the properties of proteins and influence their activities. We are investigating a particular kind of glycosylation, the addition of the disaccharide Glc-Fuc-O- to Thr/Ser residues in the consensus sequence WX5CX2/3S/TCX2G of Thrombospondin Type 1 repeats (TSRs). The Drosophila enzyme that catalyzes the first step of this reaction, O-fucosyltranferase 2 (POFUT2), was recently purified and characterized in vitro. However, the in vivo function of this enzyme remains elusive. We use the C. elegans model system to investigate the role of POFUT2 during development. We are currently characterizing a null mutant of the POFUT2 homolog in C. elegans, pad-2(tm1756). The tm1756 mutant does not have obvious defects, except for a gonadal phenotype. The anterior distal tip cell (DTC) migrates dorsally precociously. Genetic analysis showed that the components of the netrin pathway unc-5, unc-40, and unc-6 as well as daf-9 and daf-12 are epistatic to pad-2, suggesting that pad-2 acts upstream or in a parallel pathway. This notion is further supported by the observation that expression of recombinant PAD-2 both in the DTCs (driven by its own promoter or the lag-2 promoter) as well as in the body wall muscles (driven by the myo-3 promoter) rescued the early dorsal migration phenotype in the tm1756 mutant. On the other hand, recombinant PAD-2 that carries a mutation in the putative catalytic core was not able to rescue the migration phenotype. We are now focusing on three TSR-containing proteins that could mediate the PAD-2 signal at the time of DTC migration: SPON-1, GON-1 and UNC-5.}, author = {Canevascini, Stefano and Klein, Dominique and Grob, Marianne and Hess, Daniel and Kozma, Krisztina and Althaus, Jasmin and Chiquet, Ruth and Hofsteenge, Jan}, citeulike-article-id = {3333777}, citeulike-linkout-0 = {http://www.wormbase.org/db/misc/paper?name=WBPaper00030630}, journal = {International Worm Meeting}, keywords = {b02734, c\_elegans, caenorhabditis\_elegans, celegans, daf-12, daf-9, elegans, f11a13, f41c61, k10g93, k12f21, lag-2, meeting\_abstract, myo-3, nematode, pad-2, t13c51, t19b47, unc-40, unc-5, unc-6, wormbase, y73c8b4}, posted-at = {2008-09-24 20:33:00}, priority = {3}, title = {The O-fucosyltransferase POFUT2 modulates the migration of the distal tip cell in C. elegans.}, url = {http://www.wormbase.org/db/misc/paper?name=WBPaper00030630}, year = {2007} }

TY - CONF ID - citeulike:3333777 L3 - citeulike-article-id:3333777 N2 - Glycosyl-transferases add glycans to proteins that vary in structure from simple sugar chains to very complex ones. These modifications can drastically change the properties of proteins and influence their activities. We are investigating a particular kind of glycosylation, the addition of the disaccharide Glc-Fuc-O- to Thr/Ser residues in the consensus sequence WX5CX2/3S/TCX2G of Thrombospondin Type 1 repeats (TSRs). The Drosophila enzyme that catalyzes the first step of this reaction, O-fucosyltranferase 2 (POFUT2), was recently purified and characterized in vitro. However, the in vivo function of this enzyme remains elusive. We use the C. elegans model system to investigate the role of POFUT2 during development. We are currently characterizing a null mutant of the POFUT2 homolog in C. elegans, pad-2(tm1756). The tm1756 mutant does not have obvious defects, except for a gonadal phenotype. The anterior distal tip cell (DTC) migrates dorsally precociously. Genetic analysis showed that the components of the netrin pathway unc-5, unc-40, and unc-6 as well as daf-9 and daf-12 are epistatic to pad-2, suggesting that pad-2 acts upstream or in a parallel pathway. This notion is further supported by the observation that expression of recombinant PAD-2 both in the DTCs (driven by its own promoter or the lag-2 promoter) as well as in the body wall muscles (driven by the myo-3 promoter) rescued the early dorsal migration phenotype in the tm1756 mutant. On the other hand, recombinant PAD-2 that carries a mutation in the putative catalytic core was not able to rescue the migration phenotype. We are now focusing on three TSR-containing proteins that could mediate the PAD-2 signal at the time of DTC migration: SPON-1, GON-1 and UNC-5. JF - International Worm Meeting TI - The O-fucosyltransferase POFUT2 modulates the migration of the distal tip cell in C. elegans. KW - b02734 KW - c_elegans KW - caenorhabditis_elegans KW - celegans KW - daf-12 KW - daf-9 KW - elegans KW - f11a13 KW - f41c61 KW - k10g93 KW - k12f21 KW - lag-2 KW - meeting_abstract KW - myo-3 KW - nematode KW - pad-2 KW - t13c51 KW - t19b47 KW - unc-40 KW - unc-5 KW - unc-6 KW - wormbase KW - y73c8b4 AU - Canevascini, Stefano AU - Klein, Dominique AU - Grob, Marianne AU - Hess, Daniel AU - Kozma, Krisztina AU - Althaus, Jasmin AU - Chiquet, Ruth AU - Hofsteenge, Jan PY - 2007/// UR - http://www.wormbase.org/db/misc/paper?name=WBPaper00030630 ER -