10.1184/R1/6104537.v1
Elsa-Noah N'Diaye
Elsa-Noah
N'Diaye
Aylin C. Hanyaloglu
Aylin C.
Hanyaloglu
Kimberly K. Kajihara
Kimberly
K. Kajihara
Manojkumar Puthenveedu
Manojkumar
Puthenveedu
Ping Wu
Ping
Wu
Mark von Zastrow
Mark
von Zastrow
Eric J. Brown
Eric
J. Brown
The ubiquitin-like protein PLIC-2 is a negative regulator of G protein-coupled receptor endocytosis.
Carnegie Mellon University
2008
Adaptor Proteins
Signal Transducing
Vesicular Transport
Amino Acid Motifs
Arrestins
Calcium-Binding Proteins
Carrier Proteins
Cell Cycle Proteins
Cell Line
Cell Membrane
Clathrin-Coated Vesicles
Endocytosis
Humans
Intracellular Signaling Peptides and Proteins
Phosphoproteins
Protein Binding
Protein Structure
Tertiary
Protein Transport
Receptors
Adrenergic
beta-2
Vasopressin
Ubiquitins
2008-03-01 00:00:00
Journal contribution
https://kilthub.cmu.edu/articles/journal_contribution/The_ubiquitin-like_protein_PLIC-2_is_a_negative_regulator_of_G_protein-coupled_receptor_endocytosis_/6104537
<p>The activity of many signaling receptors is regulated by their endocytosis via clathrin-coated pits (CCPs). For G protein-coupled receptors (GPCRs), recruitment of the adaptor protein arrestin to activated receptors is thought to be sufficient to drive GPCR clustering in CCPs and subsequent endocytosis. We have identified an unprecedented role for the ubiquitin-like protein PLIC-2 as a negative regulator of GPCR endocytosis. Protein Linking IAP to Cytoskeleton (PLIC)-2 overexpression delayed ligand-induced endocytosis of two GPCRs: the V2 vasopressin receptor and beta-2 adrenergic receptor, without affecting endocytosis of the transferrin or epidermal growth factor receptor. The closely related isoform PLIC-1 did not affect receptor endocytosis. PLIC-2 specifically inhibited GPCR concentration in CCPs, without affecting membrane recruitment of arrestin-3 to activated receptors or its cellular levels. Depletion of cellular PLIC-2 accelerated GPCR endocytosis, confirming its regulatory function at endogenous levels. The ubiquitin-like domain of PLIC-2, a ligand for ubiquitin-interacting motifs (UIMs), was required for endocytic inhibition. Interestingly, the UIM-containing endocytic adaptors epidermal growth factor receptor protein substrate 15 and Epsin exhibited preferential binding to PLIC-2 over PLIC-1. This differential interaction may underlie PLIC-2 specific effect on GPCR endocytosis. Identification of a negative regulator of GPCR clustering reveals a new function of ubiquitin-like proteins and highlights a cellular requirement for exquisite regulation of receptor dynamics.</p>