Tetraspan cargo adaptors usher GPI-anchored proteins into multivesicular bodies

TY - JOUR

T1 - Tetraspan cargo adaptors usher GPI-anchored proteins into multivesicular bodies

AU - MacDonald, Chris

AU - Stamnes, Mark A.

AU - Katzmann, David J.

AU - Piper, Robert C.

PY - 2015/1/1

Y1 - 2015/1/1

N2 - 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 (GPIAPs) 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.

AB - 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 (GPIAPs) 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.

KW - Cos proteins

KW - GPI-anchored proteins

KW - Lysosomes

KW - Multivesicular bodies

KW - Tetraspanins

KW - Ubiquitin

KW - Vacuole

UR - http://www.scopus.com/inward/record.url?scp=84964091212&partnerID=8YFLogxK

U2 - 10.1080/15384101.2015.1100773

DO - 10.1080/15384101.2015.1100773

M3 - Article

C2 - 26505929

AN - SCOPUS:84964091212

SN - 1538-4101

VL - 14

SP - 3673

EP - 3678

JO - Cell cycle (Georgetown, Tex.)

JF - Cell cycle (Georgetown, Tex.)

IS - 23

ER -