Hrs and endocytic sorting of ubiquitinated membrane proteins.
Endocytosed receptors are either recycled to the plasma membrane or trapped within intralumenal vesicles of multi-vesicular bodies for subsequent degradation in lysosomes. How the cell is able to sort receptors in endosomes has so far been largely unknown. The hepatocyte growth factor regulated tyrosine kinase substrate, Hrs, is an essential protein that has been implicated in cell signalling and intracellular membrane trafficking. Very recently, several reports have demonstrated a role for Hrs in endocytic sorting of ubiquitinated membrane proteins. Here, we review current knowledge about how Hrs recognises ubiquitinated cargo that is destined for lysosomal degradation, and how Hrs may act as a key regulator of the molecular machinery involved in receptor sorting and multivesicular body formation.
Raiborg
Camilla
C
Department of Biochemistry, Institute for Cancer Research, Norwegian Radium Hospital, Montebello, N-0310 Oslo, Norway.
Stenmark
Harald
H
D000818:Animals; D002462:Cell Membrane / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D011956:Receptors, Cell Surface / Q000378:metabolism*; D022161:Transport Vesicles / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D056827:Endosomal Sorting Complexes Required for Transport; D010750:Phosphoproteins; D011956:Receptors, Cell Surface; D025801:Ubiquitin; C096164:hepatocyte growth factor-regulated tyrosine kinase substrate