Display Settings:


Send to:

Choose Destination
EMBO J. 2005 Jul 6;24(13):2265-83. Epub 2005 Jun 9.

Essential role of Hrs in a recycling mechanism mediating functional resensitization of cell signaling.

Author information

  • 1University of California, San Francisco, CA 94143-2140, USA.


Hepatocyte growth factor-regulated tyrosine kinase substrate (Hrs) is well known to terminate cell signaling by sorting activated receptors to the MVB/lysosomal pathway. Here we identify a distinct role of Hrs in promoting rapid recycling of endocytosed signaling receptors to the plasma membrane. This function of Hrs is specific for receptors that recycle in a sequence-directed manner, in contrast to default recycling by bulk membrane flow, and is distinguishable in several ways from previously identified membrane-trafficking functions of Hrs/Vps27p. In particular, Hrs function in sequence-directed recycling does not require other mammalian Class E gene products involved in MVB/lysosomal sorting, nor is receptor ubiquitination required. Mutational studies suggest that the VHS domain of Hrs plays an important role in sequence-directed recycling. Disrupting Hrs-dependent recycling prevented functional resensitization of the beta(2)-adrenergic receptor, converting the temporal profile of cell signaling by this prototypic G protein-coupled receptor from sustained to transient. These studies identify a novel function of Hrs in a cargo-specific recycling mechanism, which is critical to controlling functional activity of the largest known family of signaling receptors.

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (12)Free text

Figure 1ab
Figure 1cd
Figure 2ab
Figure 2cd
Figure 3
Figure 4abc
Figure 4de
Figure 4fg
Figure 5acd
Figure 5b
Figure 5e
Figure 6
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for HighWire Icon for PubMed Central
    Loading ...
    Write to the Help Desk