PH-independent endocytic cycling of the chemokine receptor CCR5

被引:23
作者
Signoret, N
Christophe, T
Oppermann, M
Marsh, M
机构
[1] UCL, MRC, Mol Cell Biol Lab, Cell Biol Unit, London WC1E 6BT, England
[2] Univ Gottingen, Dept Immunol, D-37075 Gottingen, Germany
关键词
CCR5; chemokine; chemokine receptor; endocytosis; recycling;
D O I
10.1111/j.1600-0854.2004.00200.x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Following agonist activation, the chemokine receptor CCR5 is internalised through clathrin-coated pits and delivered to recycling endosomes. Subsequently, ligand- free and resensitised receptors are recycled to the cell surface. Currently little is known of the mechanisms regulating resensitisation and recycling of this G-protein coupled receptor. Here we show that raising the pH of endocytic compartments, using bafilomycin A, monensin or NH4Cl, does not significantly affect CCR5 endocytosis, recycling or dephosphorylation. By contrast, these reagents inhibited recycling of another well-characterised G protein coupled receptor, the beta(2)-adrenergic receptor, following agonist-induced internalisation. CCR5-bound RANTES (CCL5) and MIP-1beta (CCL4) only exhibit pH-dependent dissociation at pH < 4.0, below the values normally found in endocytic organelles. Although receptor-agonist dissociation is not dependent on low pH, the subsequent degradation of released chemokine is inhibited in the presence of reagents that raise endosomal pH. Our data show that exposure to low pH is not required for RANTES or MIP-1beta dissociation from CCR5, or for recycling of internalised CCR5 to the cell surface.
引用
收藏
页码:529 / 543
页数:15
相关论文
共 33 条
[1]   HIV coreceptor downregulation as antiviral principle: SDF-1 alpha-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication [J].
Amara, A ;
LeGall, S ;
Schwartz, O ;
Salamero, J ;
Montes, M ;
Loetscher, P ;
Baggiolini, M ;
Virelizier, JL ;
ArenzanaSeisdedos, F .
JOURNAL OF EXPERIMENTAL MEDICINE, 1997, 186 (01) :139-146
[2]   A small-molecule, nonpeptide CCR5 antagonist with highly potent and selective anti-HIV-1 activity [J].
Baba, M ;
Nishimura, O ;
Kanzaki, N ;
Okamoto, M ;
Sawada, H ;
Iizawa, Y ;
Shiraishi, M ;
Aramaki, Y ;
Okonogi, K ;
Ogawa, Y ;
Meguro, K ;
Fujino, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1999, 96 (10) :5698-5703
[3]   Association of chemokine-mediated block to HIV entry with coreceptor internalization [J].
Brandt, SM ;
Mariani, R ;
Holland, AU ;
Hope, TJ ;
Landau, NR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (19) :17291-17299
[4]  
CLAGUE MJ, 1994, J BIOL CHEM, V269, P21
[5]  
Drose S, 1997, J EXP BIOL, V200, P1
[6]  
Ferguson SSG, 2001, PHARMACOL REV, V53, P1
[7]   DELINEATION OF THE ENDOCYTIC PATHWAY OF SUBSTANCE-P AND ITS 7-TRANSMEMBRANE DOMAIN NK1 RECEPTOR [J].
GRADY, EF ;
GARLAND, AM ;
GAMP, PD ;
LOVETT, M ;
PAYAN, DG ;
BUNNETT, NW .
MOLECULAR BIOLOGY OF THE CELL, 1995, 6 (05) :509-524
[8]   MEMBRANE-TRANSPORT IN THE ENDOCYTIC PATHWAY [J].
GRUENBERG, J ;
MAXFIELD, FR .
CURRENT OPINION IN CELL BIOLOGY, 1995, 7 (04) :552-563
[9]   INHIBITION OF SEMLIKI FOREST VIRUS PENETRATION BY LYSOSOMOTROPIC WEAK BASES [J].
HELENIUS, A ;
MARSH, M ;
WHITE, J .
JOURNAL OF GENERAL VIROLOGY, 1982, 58 (JAN) :47-61
[10]   Chemokine receptors [J].
Horuk, R .
CYTOKINE & GROWTH FACTOR REVIEWS, 2001, 12 (04) :313-335