Adenylyl cyclase localization regulates streaming during chemotaxis

Cell. 2003 Feb 21;112(4):549-60. doi: 10.1016/s0092-8674(03)00081-3.

Abstract

We studied the role of the adenylyl cyclase ACA in Dictyostelium discoideum chemotaxis and streaming. In this process, cells orient themselves in a head to tail fashion as they are migrating to form aggregates. We show that cells lacking ACA are capable of moving up a chemoattractant gradient, but are unable to stream. Imaging of ACA-YFP reveals plasma membrane labeling highly enriched at the uropod of polarized cells. This localization requires the actin cytoskeleton but is independent of the regulator CRAC and the effector PKA. A constitutively active mutant of ACA shows dramatically reduced uropod enrichment and has severe streaming defects. We propose that the asymmetric distribution of ACA provides a compartment from which cAMP is secreted to locally act as a chemoattractant, thereby providing a unique mechanism to amplify chemical gradients. This could represent a general mechanism that cells use to amplify chemotactic responses.

MeSH terms

  • Actins / metabolism
  • Adenylyl Cyclases / biosynthesis*
  • Animals
  • Bacterial Proteins / metabolism
  • Cells, Cultured
  • Chemotaxis*
  • Cyclic AMP / metabolism
  • Dictyostelium / metabolism
  • Dictyostelium / physiology*
  • Electroporation
  • Immunoblotting
  • Luminescent Proteins / metabolism
  • Microscopy, Confocal
  • Microscopy, Fluorescence
  • Mutation
  • Plasmids / metabolism
  • Signal Transduction
  • Subcellular Fractions / metabolism
  • Time Factors

Substances

  • Actins
  • Bacterial Proteins
  • Luminescent Proteins
  • yellow fluorescent protein, Bacteria
  • Cyclic AMP
  • Adenylyl Cyclases