PMID- 15805108
OWN - NLM
STAT- MEDLINE
DCOM- 20050929
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 280
IP  - 25
DP  - 2005 Jun 24
TI  - Receptor activity-modifying protein (RAMP) isoform-specific regulation of 
      adrenomedullin receptor trafficking by NHERF-1.
PG  - 23926-35
AB  - Receptor activity-modifying proteins (RAMPs 1-3) are single transmembrane 
      accessory proteins critical to various G-protein coupled receptors for plasma 
      membrane expression and receptor phenotype. A functional receptor for the 
      vasodilatory ligand, adrenomedullin (AM), is comprised of RAMP2 or RAMP3 and 
      calcitonin receptor-like receptor (CRLR). It is now known that RAMP3 
      protein-protein interactions regulate the recycling of the AM2 receptor. The 
      major aim of this study was to identify other interaction partners of RAMP3 and 
      determine their role in CRLR-RAMP3 trafficking. Trafficking of G-protein-coupled 
      receptors has been shown to be regulated by the Na+/H+ exchanger regulatory 
      factor-1 (NHERF-1), an adaptor protein containing two tandem 
      PSD-95/Discs-large/ZO-1 homology (PDZ) domains. In HEK 293T cells expressing the 
      AM2 receptor, the complex undergoes agonist-induced desensitization and 
      internalization. However, in the presence of NHERF-1, although the AM receptor 
      (CRLR/RAMP3) undergoes desensitization, the internalization of the receptor 
      complex is blocked. Overlay assays and mutational analysis indicated that RAMP3 
      and NHERF-1 interact via a PDZ type I domain on NHERF-1. The internalization of 
      the CRLR-RAMP complex was not affected by NHERF-1 when CRLR was co-expressed with 
      RAMP1 or RAMP2. Mutation of the ezrin/radixin/moesin (ERM) domain on NHERF-1 
      indicated that NHERF-1 inhibits CRLR/RAMP3 complex internalization by tethering 
      the complex to the actin cytoskeleton. When examined in a primary culture of 
      human proximal tubule cells endogenously expressing the CRLR-RAMP3 complex and 
      NHERF-1, the CRLR-RAMP complex desensitizes but is unable to internalize upon 
      agonist stimulation. Knock-down of either RAMP3 or NHERF-1 by RNA interference 
      technology enabled agonist-induced internalization of the CRLR-RAMP complex. 
      These results, using both endogenous and overexpressed cellular models, indicate 
      a novel function for NHERF-1 and RAMP3 in the internalization of the AM receptor 
      and suggest additional regulatory mechanisms for receptor trafficking.
FAU - Bomberger, Jennifer M
AU  - Bomberger JM
AD  - Department of Physiology, Michigan State University, East Lansing, Michigan 
      48824, USA.
FAU - Spielman, William S
AU  - Spielman WS
FAU - Hall, Carolyn S
AU  - Hall CS
FAU - Weinman, Edward J
AU  - Weinman EJ
FAU - Parameswaran, Narayanan
AU  - Parameswaran N
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20050401
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Protein Isoforms)
RN  - 0 (RAMP1 protein, human)
RN  - 0 (RAMP2 protein, human)
RN  - 0 (RAMP3 protein, human)
RN  - 0 (Receptor Activity-Modifying Protein 1)
RN  - 0 (Receptor Activity-Modifying Protein 2)
RN  - 0 (Receptor Activity-Modifying Protein 3)
RN  - 0 (Receptor Activity-Modifying Proteins)
RN  - 0 (Receptors, Adrenomedullin)
RN  - 0 (Receptors, Peptide)
RN  - 0 (Sodium-Hydrogen Exchangers)
RN  - 0 (sodium-hydrogen exchanger regulatory factor)
SB  - IM
MH  - Cell Line
MH  - Cloning, Molecular
MH  - Endocytosis
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/genetics/*physiology
MH  - Membrane Proteins/genetics/*physiology
MH  - Mutagenesis, Site-Directed
MH  - Phosphoproteins/*physiology
MH  - Protein Binding
MH  - Protein Isoforms/*physiology
MH  - Protein Transport
MH  - RNA Interference
MH  - Receptor Activity-Modifying Protein 1
MH  - Receptor Activity-Modifying Protein 2
MH  - Receptor Activity-Modifying Protein 3
MH  - Receptor Activity-Modifying Proteins
MH  - Receptors, Adrenomedullin
MH  - Receptors, Peptide/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sodium-Hydrogen Exchangers
EDAT- 2005/04/05 09:00
MHDA- 2005/09/30 09:00
CRDT- 2005/04/05 09:00
PHST- 2005/04/05 09:00 [pubmed]
PHST- 2005/09/30 09:00 [medline]
PHST- 2005/04/05 09:00 [entrez]
AID - S0021-9258(20)67450-6 [pii]
AID - 10.1074/jbc.M501751200 [doi]
PST - ppublish
SO  - J Biol Chem. 2005 Jun 24;280(25):23926-35. doi: 10.1074/jbc.M501751200. Epub 2005 
      Apr 1.