PMID- 10097102
OWN - NLM
STAT- MEDLINE
DCOM- 19990512
LR  - 20190501
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 96
IP  - 7
DP  - 1999 Mar 30
TI  - The beta2-adrenergic receptor/betaarrestin complex recruits the clathrin adaptor 
      AP-2 during endocytosis.
PG  - 3712-7
AB  - betaarrestins mediate the desensitization of the beta2-adrenergic receptor
      (beta2AR) and many other G protein-coupled receptors (GPCRs). Additionally,
      betaarrestins initiate the endocytosis of these receptors via clathrin
      coated-pits and interact directly with clathrin. Consequently, it has been
      proposed that betaarrestins serve as clathrin adaptors for the GPCR family by
      linking these receptors to clathrin lattices. AP-2, the heterotetrameric clathrin
      adaptor protein, has been demonstrated to mediate the internalization of many
      types of plasma membrane proteins other than GPCRs. AP-2 interacts with the
      clathrin heavy chain and cytoplasmic domains of receptors such as those for
      epidermal growth factor and transferrin. In the present study we demonstrate the 
      formation of an agonist-induced multimeric complex containing a GPCR,
      betaarrestin 2, and the beta2-adaptin subunit of AP-2. beta2-Adaptin binds
      betaarrestin 2 in a yeast two-hybrid assay and coimmunoprecipitates with
      betaarrestins and beta2AR in an agonist-dependent manner in HEK-293 cells.
      Moreover, beta2-adaptin translocates from the cytosol to the plasma membrane in
      response to the beta2AR agonist isoproterenol and colocalizes with beta2AR in
      clathrin-coated pits. Finally, expression of betaarrestin 2 minigene constructs
      containing the beta2-adaptin interacting region inhibits beta2AR endocytosis.
      These findings point to a role for AP-2 in GPCR endocytosis, and they suggest
      that AP-2 functions as a clathrin adaptor for the endocytosis of diverse classes 
      of membrane receptors.
FAU - Laporte, S A
AU  - Laporte SA
AD  - Howard Hughes Medical Institute Laboratories and Department of Cell Biology, Duke
      University Medical Center, Durham, NC 27710, USA.
FAU - Oakley, R H
AU  - Oakley RH
FAU - Zhang, J
AU  - Zhang J
FAU - Holt, J A
AU  - Holt JA
FAU - Ferguson, S S
AU  - Ferguson SS
FAU - Caron, M G
AU  - Caron MG
FAU - Barak, L S
AU  - Barak LS
LA  - eng
GR  - R01 NS019576/NS/NINDS NIH HHS/United States
GR  - HL 03422/HL/NHLBI NIH HHS/United States
GR  - NS 19576/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (AP2B1 protein, human)
RN  - 0 (Adaptor Protein Complex alpha Subunits)
RN  - 0 (Adaptor Protein Complex beta Subunits)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Arrestins)
RN  - 0 (Luminescent Proteins)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Membrane Proteins)
RN  - 0 (Receptors, Adrenergic, beta-2)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (beta-Arrestins)
RN  - 147336-22-9 (Green Fluorescent Proteins)
SB  - IM
MH  - Adaptor Protein Complex alpha Subunits
MH  - Adaptor Protein Complex beta Subunits/chemistry/genetics/*physiology
MH  - Adaptor Proteins, Vesicular Transport
MH  - Amino Acid Sequence
MH  - Animals
MH  - Arrestins/genetics/*physiology
MH  - COS Cells
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Endocytosis/*physiology
MH  - Green Fluorescent Proteins
MH  - Humans
MH  - Luminescent Proteins/biosynthesis/chemistry/genetics
MH  - Macromolecular Substances
MH  - Membrane Proteins/chemistry/genetics/*physiology
MH  - Molecular Sequence Data
MH  - Receptors, Adrenergic, beta-2/genetics/*physiology
MH  - Recombinant Fusion Proteins/biosynthesis
MH  - Saccharomyces cerevisiae
MH  - Transfection
MH  - beta-Arrestins
PMC - PMC22359
EDAT- 1999/03/31 00:00
MHDA- 1999/03/31 00:01
CRDT- 1999/03/31 00:00
PHST- 1999/03/31 00:00 [pubmed]
PHST- 1999/03/31 00:01 [medline]
PHST- 1999/03/31 00:00 [entrez]
AID - 10.1073/pnas.96.7.3712 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3712-7. doi: 10.1073/pnas.96.7.3712.