PMID- 10228153
OWN - NLM
STAT- MEDLINE
DCOM- 19990628
LR  - 20181113
IS  - 0261-4189 (Print)
IS  - 0261-4189 (Linking)
VI  - 18
IP  - 9
DP  - 1999 May 4
TI  - PDZ-mediated interactions retain the epithelial GABA transporter on the
      basolateral surface of polarized epithelial cells.
PG  - 2384-93
AB  - The PDZ target motifs located in the C-terminal end of many receptors and ion
      channels mediate protein-protein interactions by binding to specific
      PDZ-containing proteins. These interactions are involved in the localization of
      surface proteins on specialized membrane domains of neuronal and epithelial
      cells. However, the molecular mechanism responsible for this PDZ
      protein-dependent polarized localization is still unclear. This study first
      demonstrated that the epithelial gamma-aminobutyric acid (GABA) transporter
      (BGT-1) contains a PDZ target motif that mediates the interaction with the PDZ
      protein LIN-7 in Madin-Darby canine kidney (MDCK) cells, and then investigated
      the role of this interaction in the basolateral localization of the transporter. 
      It was found that although the transporters from which the PDZ target motif was
      deleted were still targeted to the basolateral surface, they were not retained
      but internalized in an endosomal recycling compartment. Furthermore, an
      interfering BGT peptide determined the intracellular relocation of the native
      transporter. These data indicate that interactions with PDZ proteins determine
      the polarized surface localization of target proteins by means of retention and
      not targeting mechanisms. PDZ proteins may, therefore, act as a sort of membrane 
      protein sorting machinery which, by recognizing retention signals (the PDZ target
      sequences), prevents protein internalization.
FAU - Perego, C
AU  - Perego C
AD  - CNR Cellular and Molecular Pharmacology Center, Department of Pharmacology,
      University of Milan, Via Vanvitelli 32, 20129 Milan, Italy.
FAU - Vanoni, C
AU  - Vanoni C
FAU - Villa, A
AU  - Villa A
FAU - Longhi, R
AU  - Longhi R
FAU - Kaech, S M
AU  - Kaech SM
FAU - Frohli, E
AU  - Frohli E
FAU - Hajnal, A
AU  - Hajnal A
FAU - Kim, S K
AU  - Kim SK
FAU - Pietrini, G
AU  - Pietrini G
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Carrier Proteins)
RN  - 0 (GABA Plasma Membrane Transport Proteins)
RN  - 0 (LIN-7 protein, mammalian)
RN  - 0 (Membrane Proteins)
RN  - 0 (Membrane Transport Proteins)
RN  - 0 (Organic Anion Transporters)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Carrier Proteins/*metabolism
MH  - *Cell Polarity
MH  - Cells, Cultured
MH  - Dogs
MH  - Epithelial Cells/*metabolism
MH  - GABA Plasma Membrane Transport Proteins
MH  - Kidney/cytology
MH  - Membrane Proteins/*metabolism
MH  - *Membrane Transport Proteins
MH  - Molecular Sequence Data
MH  - *Organic Anion Transporters
MH  - Protein Binding
PMC - PMC1171321
EDAT- 1999/05/06 00:00
MHDA- 1999/05/06 00:01
CRDT- 1999/05/06 00:00
PHST- 1999/05/06 00:00 [pubmed]
PHST- 1999/05/06 00:01 [medline]
PHST- 1999/05/06 00:00 [entrez]
AID - 10.1093/emboj/18.9.2384 [doi]
PST - ppublish
SO  - EMBO J. 1999 May 4;18(9):2384-93. doi: 10.1093/emboj/18.9.2384.