Protein kinase A, which regulates intracellular transport, forms complexes with molecular motors on organelles

Curr Biol. 2004 Oct 26;14(20):1877-81. doi: 10.1016/j.cub.2004.10.003.

Abstract

Major signaling cascades have been shown to play a role in the regulation of intracellular organelle transport . Aggregation and dispersion of pigment granules in melanophores are regulated by the second messenger cAMP through the protein kinase A (PKA) signaling pathway ; however, the exact mechanisms of this regulation are poorly understood. To study the role of signaling molecules in the regulation of pigment transport in melanophores, we have asked the question whether the components of the cAMP-signaling pathway are bound to pigment granules and whether they interact with molecular motors to regulate the granule movement throughout the cytoplasm. We found that purified pigment granules contain PKA and scaffolding proteins and that PKA associates with pigment granules in cells. Furthermore, we found that the PKA regulatory subunit forms two separate complexes, one with cytoplasmic dynein ("aggregation complex") and one with kinesin II and myosin V ("dispersion complex"), and that the removal of PKA from granules causes dissociation of dynein and disruption of dynein-dependent pigment aggregation. We conclude that cytoplasmic organelles contain protein complexes that include motor proteins and signaling molecules involved in different components of intracellular transport. We propose to call such complexes 'regulated motor units' (RMU).

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Biological Transport / physiology
  • Calcium-Binding Proteins / metabolism
  • Cell Line
  • Cyclic AMP-Dependent Protein Kinases / metabolism*
  • Dyneins / metabolism
  • Immunoblotting
  • Immunoprecipitation
  • Kinesin
  • Melanophores / metabolism*
  • Microinjections
  • Molecular Motor Proteins / metabolism*
  • Muscle Proteins / metabolism
  • Myosin Type V / metabolism
  • Organelles / physiology*
  • Pigments, Biological / metabolism*
  • Signal Transduction / physiology*
  • Transfection
  • Xenopus
  • Xenopus Proteins

Substances

  • Calcium-Binding Proteins
  • Molecular Motor Proteins
  • Muscle Proteins
  • Pigments, Biological
  • XKLP3 protein, Xenopus
  • Xenopus Proteins
  • kinesin-II
  • Cyclic AMP-Dependent Protein Kinases
  • Myosin Type V
  • Dyneins
  • Kinesin