PMID- 19000035
OWN - NLM
STAT- MEDLINE
DCOM- 20090115
LR  - 20081222
IS  - 1470-8728 (Electronic)
IS  - 0264-6021 (Linking)
VI  - 417
IP  - 2
DP  - 2009 Jan 15
TI  - A novel role of the C-terminus of b 0,+ AT in the ER-Golgi trafficking of the 
      rBAT-b 0,+ AT heterodimeric amino acid transporter.
PG  - 441-8
LID - 10.1042/BJ20081798 [doi]
AB  - The heterodimeric complex composed of rBAT (related to b(0,+) amino acid 
      transporter), a single-membrane-spanning glycosylated heavy chain, and b(0,+)AT, 
      a putative 12-membrane-spanning non-glycosylated light chain, is an amino acid 
      transporter that mediates the activity of system b(0,+), a major apical transport 
      system for cystine and dibasic amino acids in renal proximal tubule and small 
      intestine. The C-terminus of b(0,+)AT has been proposed to play an important role 
      in the functional expression of the heterodimeric transporters. In the present 
      study, to reveal the roles of the C-terminus, we analysed b(0,+)AT mutants whose 
      C-termini were sequentially deleted or replaced by site-directed mutagenesis in 
      polarized MDCKII (Madin-Darby canine kidney II), non-polarized HEK-293 (human 
      embryonic kidney-293) and HeLa cells. Although the deletion of C-terminus of 
      b(0,+)AT did not affect the formation of a heterodimer with rBAT, it resulted in 
      the loss of apparent transport function, owing to the failure of the 
      plasma-membrane targeting of rBAT-b(0,+)AT heterodimeric complex associated with 
      incomplete glycosylation of rBAT. A motif-like sequence 
      Val(480)-Pro(481)-Pro(482) was identified in the C-terminus of b(0,+)AT to be 
      responsible for the C-terminus action in promoting the trafficking of 
      rBAT-b(0,+)AT heterodimeric complex from the ER (endoplasmic reticulum) to Golgi 
      apparatus. This is, to our knowledge, the first demonstration of the active 
      contribution of the C-terminus of a light-chain subunit to the intracellular 
      trafficking of heterodimeric transporters. Because the motif-like sequence 
      Val(480)-Pro(481)-Pro(482) is well conserved among the C-termini of light-chain 
      subunits, common regulatory mechanisms could be proposed among heterodimeric 
      amino acid transporters.
FAU - Sakamoto, Shinichi
AU  - Sakamoto S
AD  - Department of Pharmacology and Toxicology, Kyorin University School of Medicine, 
      Tokyo, Japan.
FAU - Chairoungdua, Arthit
AU  - Chairoungdua A
FAU - Nagamori, Shushi
AU  - Nagamori S
FAU - Wiriyasermkul, Pattama
AU  - Wiriyasermkul P
FAU - Promchan, Kanyarat
AU  - Promchan K
FAU - Tanaka, Hidekazu
AU  - Tanaka H
FAU - Kimura, Toru
AU  - Kimura T
FAU - Ueda, Takeshi
AU  - Ueda T
FAU - Fujimura, Masaaki
AU  - Fujimura M
FAU - Shigeta, Yasuhiro
AU  - Shigeta Y
FAU - Naya, Yukio
AU  - Naya Y
FAU - Akakura, Koichiro
AU  - Akakura K
FAU - Ito, Haruo
AU  - Ito H
FAU - Endou, Hitoshi
AU  - Endou H
FAU - Ichikawa, Tomohiko
AU  - Ichikawa T
FAU - Kanai, Yoshikatsu
AU  - Kanai Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biochem J
JT  - The Biochemical journal
JID - 2984726R
RN  - 0 (Amino Acid Transport Systems)
SB  - IM
CIN - Biochem J. 2009 Jan 15;417(2):e9-11. PMID: 19099537
MH  - Amino Acid Sequence
MH  - Amino Acid Transport Systems/chemistry/genetics/*metabolism
MH  - Cell Line
MH  - Endoplasmic Reticulum/*metabolism
MH  - Gene Deletion
MH  - Glycosylation
MH  - Golgi Apparatus/*metabolism
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutation/genetics
MH  - *Protein Multimerization
MH  - Protein Transport
MH  - Sequence Alignment
EDAT- 2008/11/13 09:00
MHDA- 2009/01/16 09:00
CRDT- 2008/11/13 09:00
PHST- 2008/11/13 09:00 [pubmed]
PHST- 2009/01/16 09:00 [medline]
PHST- 2008/11/13 09:00 [entrez]
AID - BJ20081798 [pii]
AID - 10.1042/BJ20081798 [doi]
PST - ppublish
SO  - Biochem J. 2009 Jan 15;417(2):441-8. doi: 10.1042/BJ20081798.