Regulation of angiotensin II type 1A receptor intracellular retention, degradation, and recycling by Rab5, Rab7, and Rab11 GTPases

被引:98
作者
Dale, LB
Seachrist, JL
Babwah, AV
Ferguson, SSG
机构
[1] John P Robarts Res Inst, Cell Biol Res Grp, London, ON N6A 5K8, Canada
[2] Univ Western Ontario, Dept Physiol & Pharmacol, London, ON N6A 5C1, Canada
关键词
D O I
10.1074/jbc.M313333200
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
Previous studies have demonstrated that the interaction of the angiotensin II type 1A receptor (AT(1A)R) carboxylterminal tail with Rab5a may modulate Rab5a activity, leading to the homotypic fusion of endocytic vesicles. Therefore, we have investigated whether AT(1A)R/Rab5a interactions mediate the retention of AT(1A)R.beta-arrestin complexes in early endosomes and whether the overexpression of Rab7 and Rab11 GTPases influences AT(1A)R lysosomal degradation and plasma membrane recycling. We found that internalized AT(1A)R was retained in Rab5a-positive early endosomes and was neither targeted to lysosomes nor recycled back to the cell surface, whereas a mutant defective in Rab5a binding, AT(1A)R-(1 - 349), was targeted to lysosomes for degradation. However, the loss of Rab5a binding to the AT(1A)R carboxyl-terminal tail did not promote AT(1A)R recycling. Rather, it was the stable binding of beta-arrestin to the AT(1A)R that prevented, at least in part, AT1AR recycling. The overexpression of wild-type Rab7 and Rab7-Q67L resulted in both increased AT(1A)R degradation and AT(1A)R targeting to lysosomes. The Rab7 expression-dependent transition of "putative" AT(1A)R.beta-arrestin complexes to late endosomes was blocked by the expression of dominant-negative Rab5a-S34N. Rab11 overexpression established AT(1A)R recycling and promoted the redistribution of AT(1A)R.beta-arrestin complexes from early to recycling endosomes. Taken together, our data suggest that Rab5, Rab7, and Rab11 work in concert with one another to regulate the intracellular trafficking patterns of the AT(1A)R.
引用
收藏
页码:13110 / 13118
页数:9
相关论文
共 40 条
[1]   Receptor/β-arrestin complex formation and the differential trafficking and resensitization of β2-adrenergic and angiotensin II type 1A receptors [J].
Anborgh, PH ;
Seachrist, JL ;
Dale, LB ;
Ferguson, SSG .
MOLECULAR ENDOCRINOLOGY, 2000, 14 (12) :2040-2053
[2]   The dynamin-dependent, arrestin-independent internalization of 5-hydroxytryptamine 2A (5-HT2A) serotonin receptors reveals differential sorting of arrestins and 5-HT2A receptors during endocytosis [J].
Bhatnagar, A ;
Willins, DL ;
Gray, JA ;
Woods, J ;
Benovic, JL ;
Roth, BL .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (11) :8269-8277
[3]   Rab7: A key to lysosome biogenesis [J].
Bucci, C ;
Thomsen, P ;
Nicoziani, P ;
McCarthy, J ;
van Deurs, B .
MOLECULAR BIOLOGY OF THE CELL, 2000, 11 (02) :467-480
[4]   LOCALIZATION OF LOW-MOLECULAR-WEIGHT GTP BINDING-PROTEINS TO EXOCYTIC AND ENDOCYTIC COMPARTMENTS [J].
CHAVRIER, P ;
PARTON, RG ;
HAURI, HP ;
SIMONS, K ;
ZERIAL, M .
CELL, 1990, 62 (02) :317-329
[5]   Differential regulation of CXCR2 trafficking by Rab GTPases [J].
Fan, GH ;
Lapierre, LA ;
Goldenring, JR ;
Richmond, A .
BLOOD, 2003, 101 (06) :2115-2124
[6]  
Ferguson SSG, 2001, PHARMACOL REV, V53, P1
[7]   Role of beta-arrestin in mediating agonist-promoted G protein-coupled receptor internalization [J].
Ferguson, SSG ;
Downey, WE ;
Colapietro, AM ;
Barak, LS ;
Menard, L ;
Caron, MG .
SCIENCE, 1996, 271 (5247) :363-366
[8]   β-arrestin- and dynamin-dependent endocytosis of the AT1 angiotensin receptor [J].
Gáborik, Z ;
Szaszák, M ;
Szidonya, L ;
Balla, B ;
Paku, S ;
Catt, KJ ;
Clark, AJL ;
Hunyady, L .
MOLECULAR PHARMACOLOGY, 2001, 59 (02) :239-247
[9]   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
[10]  
HUNYADY L, 1994, J BIOL CHEM, V269, P31378