Tetraspan cargo adaptors usher GPI-anchored proteins into multivesicular bodies.
Ubiquitinated membrane proteins are sorted into intralumenal endosomal vesicles on their way for degradation in lysosomes. Here we summarize the discovery of the Cos proteins, which work to organize and segregate ubiquitinated cargo prior to its incorporation into intralumenal vesicles of the multivesicular body (MVB). Importantly, cargoes such as GPI-anchored proteins (GPI-APs) that cannot undergo ubiquitination, rely entirely on Cos proteins for sorting into intralumenal vesicles using the same pathway that depends on ESCRTs and ubiquitin ligases that typical polytopic membrane proteins do. Here we show Cos proteins provide functions as not only adaptor proteins for ubiquitin ligases, but also as cargo carriers that can physically usher a variety of other proteins into the MVB pathway. We then discuss the significance of this new sorting model and the broader implications for this cargo adaptor mechanism, whereby yeast Cos proteins, and their likely animal analogs, provide a ubiquitin sorting signal in trans to enable sorting of a membrane protein network into intralumenal vesicles.
a Molecular Physiology and Biophysics; University of Iowa ; Iowa City , IA USA.
Chris
C
MacDonald
a Molecular Physiology and Biophysics; University of Iowa ; Iowa City , IA USA.
Mark A
MA
Stamnes
b Biochemistry and Molecular Biology; Mayo Clinic College of Medicine ; Rochester , MN USA.
David J
DJ
Katzmann
a Molecular Physiology and Biophysics; University of Iowa ; Iowa City , IA USA.
Robert C
RC
Piper
D058851:GPI-Linked Proteins / Q000378:metabolism*; D008954:Models, Biological; D057146:Multivesicular Bodies / Q000378:metabolism*; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D059470:Tetraspanins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*
D058851:GPI-Linked Proteins; D029701:Saccharomyces cerevisiae Proteins; D059470:Tetraspanins
Cos proteins; GPI-anchored proteins; Tetraspanins; lysosomes; multivesicular bodies; ubiquitin; vacuole