title: A spatially restricted increase in receptor mobility is involved in directional sensing during Dictyostelium discoideum chemotaxis.
abstract: The directed cell migration towards a chemotactic source, chemotaxis, involves three complex and interrelated processes: directional sensing, cell polarization and motility. Directional sensing allows migrating eukaryotic cells to chemotax in extremely shallow gradients (<2% across the cell body) of the chemoattractant. Although directional sensing has been observed as spatially restricted responses along the plasma membrane, our understanding of the ;compass' of the cell that controls the gradient-induced translocation of proteins during chemotactic movements is still largely lacking. Until now, the dynamical behaviour and mobility of the chemoattractant-receptor molecule has been neglected in models describing the directional sensing mechanisms. Here, we show by single-molecule microscopy an agonist-induced increase in the mobile fraction of cAMP-receptor at the leading edge of chemotacting Dictyostelium discoideum cells. The onset of receptor mobility was correlated to the uncoupling and activation of the Galpha2-protein. A finite-element simulation showed that the increase in mobile fraction of the activated receptor enabled the amplified generation of activated Gbetagamma-dimers at the leading edge of the cell, faithfully representing a primary linear amplification step in directional sensing. We propose here that modulation of the receptor mobility is directly involved in directional sensing and provides a new mechanistic basis for the primary amplification step in current theoretical models that describe directional sensing.
authors.affiliation: Physics of Life Processes, Leiden Institute of Physics, Leiden University, Niels Bohrweg 2, 2333 CA Leiden, The Netherlands.
authors.forename: Sandra
authors.initials: S
authors.lastname: de Keijzer
authors.forename: Arnauld
authors.initials: A
authors.lastname: Sergé
authors.forename: Freek
authors.initials: F
authors.lastname: van Hemert
authors.forename: Piet H M
authors.initials: PH
authors.lastname: Lommerse
authors.forename: Gerda E M
authors.initials: GE
authors.lastname: Lamers
authors.forename: Herman P
authors.initials: HP
authors.lastname: Spaink
authors.forename: Thomas
authors.initials: T
authors.lastname: Schmidt
authors.forename: B Ewa
authors.initials: BE
authors.lastname: Snaar-Jagalska
mesh_terms: D000818:Animals; D002630:Chemotactic Factors / Q000378:metabolism*; D002633:Chemotaxis / Q000502:physiology*; D004023:Dictyostelium / Q000166:cytology / Q000502:physiology*; D019281:Dimerization; D044385:GTP-Binding Protein alpha Subunits / Q000378:metabolism; D044387:GTP-Binding Protein beta Subunits / Q000378:metabolism; D044388:GTP-Binding Protein gamma Subunits / Q000378:metabolism; D015800:Protozoan Proteins / Q000378:metabolism*; D011953:Receptors, Cyclic AMP / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism
chemical_list: D002630:Chemotactic Factors; D044385:GTP-Binding Protein alpha Subunits; D044387:GTP-Binding Protein beta Subunits; D044388:GTP-Binding Protein gamma Subunits; D015800:Protozoan Proteins; D011953:Receptors, Cyclic AMP; D011993:Recombinant Fusion Proteins; C068125:cyclic AMP receptor cAR1