title: Requirement of a vasodilator-stimulated phosphoprotein family member for cell adhesion, the formation of filopodia, and chemotaxis in dictyostelium.
abstract: We have examined the function of a member of the vasodilator-stimulated phosphoprotein family of proteins (DdVASP) in Dictyostelium. Ddvasp null cells lack filopodia, whereas targeting DdVASP to the plasma membrane with a myristoyl tag results in a significant increase in filopodia. The proline-rich domain-Ena/VASP homology 2 structure is required for both actin polymerization activity and filopodia formation. Ddvasp null cells exhibit a chemotaxis defect, which appears to be due to a defect in the ability of the cells to properly adhere to the substratum and to suppress lateral pseudopod extension. We demonstrate that during chemotaxis, the anterior approximately 50% of the cell lifts from the substratum and remains elevated for up to 1 min. These defects lead to a significant decrease in chemotaxis efficiency. DdVASP localizes to the leading edge in migrating cells and to the tips of filopodia. In addition, Ddvasp null cells have a defect in particle adhesion but internalize particles normally. Our results provide new insights into the function of DdVASP in controlling the actin cytoskeleton during chemotaxis and filopodia formation.
authors.affiliation: Section of Cell and Developmental Biology, Division of Biological Sciences, Center for Molecular Genetics, University of California-San Diego, 9500 Gilman Drive, La Jolla, California 92093-0634, USA.
authors.forename: Young-Hoon
authors.initials: YH
authors.lastname: Han
authors.forename: Chang Y
authors.initials: CY
authors.lastname: Chung
authors.forename: Deborah
authors.initials: D
authors.lastname: Wessels
authors.forename: Stephen
authors.initials: S
authors.lastname: Stephens
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Titus
authors.forename: David R
authors.initials: DR
authors.lastname: Soll
authors.forename: Richard A
authors.initials: RA
authors.lastname: Firtel
mesh_terms: D000199:Actins / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000378:metabolism / Q000502:physiology*; D002633:Chemotaxis; D003001:Cloning, Molecular; D000242:Cyclic AMP / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism; D004023:Dictyostelium / Q000378:metabolism / Q000502:physiology*; D017353:Gene Deletion; D049452:Green Fluorescent Proteins; D006801:Humans; D007700:Kinetics; D008164:Luminescent Proteins / Q000378:metabolism; D008840:Microfilament Proteins; D008954:Models, Biological; D008969:Molecular Sequence Data; D009068:Movement; D010455:Peptides / Q000737:chemistry; D010587:Phagocytosis; D010750:Phosphoproteins / Q000378:metabolism* / Q000502:physiology*; D011233:Precipitin Tests; D011392:Proline / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011554:Pseudopodia / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*; D000098662:Vasodilator-Stimulated Phosphoprotein
chemical_list: D000199:Actins; D015815:Cell Adhesion Molecules; D008164:Luminescent Proteins; D008840:Microfilament Proteins; D010455:Peptides; D010750:Phosphoproteins; D011993:Recombinant Fusion Proteins; D014665:Vasodilator Agents; D000098662:Vasodilator-Stimulated Phosphoprotein; D049452:Green Fluorescent Proteins; D011392:Proline; D000242:Cyclic AMP