Oligomerization as a determinant of transporter function and trafficking

被引:104
作者
Sitte, HH [1 ]
Farhan, H
Javitch, JA
机构
[1] Med Univ Vienna, Inst Pharmacol, A-1090 Vienna, Austria
[2] Columbia Univ Coll Phys & Surg, Ctr Mol Recognit, New York, NY 10032 USA
[3] Columbia Univ Coll Phys & Surg, Dept Psychiat, New York, NY 10032 USA
[4] Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA
关键词
D O I
10.1124/mi.4.1.38
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Constitutive oligomer formation appears to be the rule for the neurotransmitter:sodium symporter (NSS) family of proteins. The propensity to form oligomers is a prerequisite for NSS proteins to pass the rigid mechanisms of quality control in the endoplasmic rebculum. Moreover, recent findings suggest that correct trafficking to the plasma membrane appears to rely on the interaction of NSS homo-oligomers with components of the COPII-vesicle machinery. The transporters present at the plasma membrane are most likely organized in a tetrameric arrangement, as a dinner of dimers. In this review, we will address ongoing efforts to unravel the underlying mechanisms of oligomer formation at the molecular and cellular levels, and we will discuss oligomerization in terms of transporter function.
引用
收藏
页码:38 / 47
页数:10
相关论文
共 76 条
[21]   Symmetrical dimer of the human dopamine transporter revealed by cross-linking Cys-306 at the extracellular end of the sixth transmembrane segment [J].
Hastrup, H ;
Karlin, A ;
Javitch, JA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (18) :10055-10060
[22]   DIMERIZATION OF CELL-SURFACE RECEPTORS IN SIGNAL-TRANSDUCTION [J].
HELDIN, CH .
CELL, 1995, 80 (02) :213-223
[23]   Surface-localized glycine transporters 1 and 2 function as monomeric proteins in Xenopus oocytes [J].
Horiuchi, M ;
Nicke, A ;
Gomeza, J ;
Aschrafi, A ;
Schmalzing, G ;
Betz, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (04) :1448-1453
[24]   Neurotransmitter transporters: fruitful targets for CNS drug discovery [J].
Iversen, L .
MOLECULAR PSYCHIATRY, 2000, 5 (04) :357-362
[25]   FRET imaging [J].
Jares-Erijman, EA ;
Jovin, TM .
NATURE BIOTECHNOLOGY, 2003, 21 (11) :1387-1395
[26]   The membrane-bound rat serotonin transporter, SERT1, is an oligomeric protein [J].
Jess, U ;
Betz, H ;
Schloss, P .
FEBS LETTERS, 1996, 394 (01) :44-46
[27]  
JUST H, 2003, J BIOL CHEM
[28]   Oligomerization of serotonin transporter and its functional consequences [J].
Kilic, F ;
Rudnick, G .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (07) :3106-3111
[29]   Dominant negative isoform of rat norepinephrine transporter produced by alternative RNA splicing [J].
Kitayama, S ;
Ikeda, T ;
Mitsuhata, C ;
Sato, T ;
Morita, K ;
Dohi, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (16) :10731-10736
[30]   MEMBRANE-PROTEIN OLIGOMERIC STRUCTURE AND TRANSPORT FUNCTION [J].
KLINGENBERG, M .
NATURE, 1981, 290 (5806) :449-454