Publication

Daydreamer, a Ras effector and GSK-3 substrate, is important for directional sensing and cell motility

Koelsch, V., Shen, Z., Lee, S., Plak, K., Lotfi, P., Chang, J., Charest, P. G., Romero, J. L., Jeon, T. J., Kortholt, A., Briggs, S. P. & Firtel, R. A., 15-Jan-2013, In : Molecular Biology of the Cell. 24, 2, p. 100-114 15 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Verena Koelsch
  • Zhouxin Shen
  • Susan Lee
  • Katarzyna Plak
  • Pouya Lotfi
  • Jessica Chang
  • Pascale G. Charest
  • Jesus Lacal Romero
  • Taeck J. Jeon
  • Arjan Kortholt
  • Steven P. Briggs
  • Richard A. Firtel

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.

Original languageEnglish
Pages (from-to)100-114
Number of pages15
JournalMolecular Biology of the Cell
Volume24
Issue number2
Publication statusPublished - 15-Jan-2013

    Keywords

  • GLYCOGEN-SYNTHASE KINASE-3, DEPENDENT PROTEIN-KINASE, RABBIT SKELETAL-MUSCLE, DICTYOSTELIUM-DISCOIDEUM, MEDIATES CHEMOTAXIS, ACTIN CYTOSKELETON, SIGNALING PATHWAYS, STAT PROTEIN, ACTIVATION, POLARITY

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