Hrs function: viruses provide the clue.
The endosomal protein Hrs plays a central role in the downregulation of receptors. A set of recent studies reveals a link between Hrs and the multiprotein complex ESCRT (endosome-associated complex required for transport) machinery that promotes inward vesiculation at the limiting membrane of the sorting endosome. A conserved sequence motif, PT/(S)AP, found in structural proteins of several RNA viruses (e.g. HIV Gag) promotes release of virus from the cell by recruiting the ESCRT machinery to the viral budding sites at the plasma membrane. The same motif is also found in Hrs and recruits the ESCRT I complex to endosomes through direct interaction with one of its components called TSG101. Fusion of Hrs with the gag gene of HIV-1 lacking this motif can complement a defect in virus budding. Further challenging data indicate a wider role for Hrs in the regulation of endosome dynamics.
Clague
Michael J
MJ
Physiological Laboratory, University of Liverpool, Crown Street, L69 3BX, Liverpool, UK. clague@liv.ac.uk
Urbé
Sylvie
S
D020816:Amino Acid Motifs; D004268:DNA-Binding Proteins / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D010750:Phosphoproteins / Q000502:physiology*; D012328:RNA Viruses / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*; D014157:Transcription Factors / Q000378:metabolism; D014779:Virus Replication; D017201:Virus Shedding; D000099177:Tsg101 Protein
D004268:DNA-Binding Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; D014157:Transcription Factors; D000099177:Tsg101 Protein; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate