title: Daydreamer, a Ras effector and GSK-3 substrate, is important for directional sensing and cell motility.
abstract: How independent signaling pathways are integrated to holistically control a biological process is not well understood. We have identified Daydreamer (DydA), a new member of the Mig10/RIAM/lamellipodin (MRL) family of adaptor proteins that localizes to the leading edge of the cell. DydA is a putative Ras effector that is required for cell polarization and directional movement during chemotaxis. dydA(-) cells exhibit elevated F-actin and assembled myosin II (MyoII), increased and extended phosphoinositide-3-kinase (PI3K) activity, and extended phosphorylation of the activation loop of PKB and PKBR1, suggesting that DydA is involved in the negative regulation of these pathways. DydA is phosphorylated by glycogen synthase kinase-3 (GSK-3), which is required for some, but not all, of DydA's functions, including the proper regulation of PKB and PKBR1 and MyoII assembly. gskA(-) cells exhibit very strong chemotactic phenotypes, as previously described, but exhibit an increased rate of random motility. gskA(-) cells have a reduced MyoII response and a reduced level of phosphatidylinositol (3,4,5)-triphosphate production, but a highly extended recruitment of PI3K to the plasma membrane and highly extended kinetics of PKB and PKBR1 activation. Our results demonstrate that GSK-3 function is essential for chemotaxis, regulating multiple substrates, and that one of these effectors, DydA, plays a key function in the dynamic regulation of chemotaxis.
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093-0380, USA.
authors.forename: Verena
authors.initials: V
authors.lastname: Kölsch
authors.forename: Zhouxin
authors.initials: Z
authors.lastname: Shen
authors.forename: Susan
authors.initials: S
authors.lastname: Lee
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Plak
authors.forename: Pouya
authors.initials: P
authors.lastname: Lotfi
authors.forename: Jessica
authors.initials: J
authors.lastname: Chang
authors.forename: Pascale G
authors.initials: PG
authors.lastname: Charest
authors.forename: Jesus Lacal
authors.initials: JL
authors.lastname: Romero
authors.forename: Taeck J
authors.initials: TJ
authors.lastname: Jeon
authors.forename: Arjan
authors.initials: A
authors.lastname: Kortholt
authors.forename: Steven P
authors.initials: SP
authors.lastname: Briggs
authors.forename: Richard A
authors.initials: RA
authors.lastname: Firtel
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D016764:Cell Polarity; D002633:Chemotaxis; D016384:Consensus Sequence; D004023:Dictyostelium / Q000166:cytology / Q000378:metabolism*; D055786:Gene Knockout Techniques; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D007700:Kinetics; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020827:rap1 GTP-Binding Proteins / Q000378:metabolism; D018631:ras Proteins / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D015800:Protozoan Proteins; D038362:Glycogen Synthase Kinase 3; D020827:rap1 GTP-Binding Proteins; D018631:ras Proteins