Vps9 domain-containing proteins: activators of Rab5 GTPases from yeast to neurons

Trends Cell Biol. 2006 Jan;16(1):27-35. doi: 10.1016/j.tcb.2005.11.001. Epub 2005 Dec 2.


Endocytosis of cell surface receptors plays an important role in regulating cell signaling cascades. In some cases, internalization of an activated receptor attenuates the signaling process, while in other cases the clustering of activated receptors on early endosomal structures has been proposed to be essential for fully activating signaling cascades. Regulating the movement of receptors and other signaling proteins through the endocytic pathway, therefore, has a direct impact on cellular homeostasis. The small GTPase Rab5 is a crucial regulatory component of the endocytic pathway. Activation of Rab5 is mediated by GDP-GTP exchange factors (GEFs) that generate the Rab5-GTP complex. A large number of proteins have been identified that contain a specific, highly conserved domain (Vps9) that catalyzes nucleotide exchange on Rab5, linking the regulation of cell signaling cascades with intracellular receptor trafficking through the endocytic pathway.

Publication types

  • Review

MeSH terms

  • Animals
  • Carrier Proteins / chemistry
  • Carrier Proteins / physiology
  • Endocytosis*
  • Enzyme Activation
  • Guanine Nucleotide Exchange Factors / chemistry
  • Guanine Nucleotide Exchange Factors / physiology
  • Humans
  • Intracellular Signaling Peptides and Proteins / chemistry
  • Intracellular Signaling Peptides and Proteins / physiology
  • Neurons / physiology*
  • Protein Structure, Tertiary*
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / physiology
  • Signal Transduction
  • Ubiquitin / physiology
  • Vesicular Transport Proteins / chemistry
  • Vesicular Transport Proteins / physiology*
  • Yeasts / physiology*
  • rab5 GTP-Binding Proteins / chemistry
  • rab5 GTP-Binding Proteins / physiology*


  • Carrier Proteins
  • Guanine Nucleotide Exchange Factors
  • Intracellular Signaling Peptides and Proteins
  • Receptors, Cell Surface
  • Ubiquitin
  • Vesicular Transport Proteins
  • rab5 GTP-Binding Proteins