کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10803091 | 1055772 | 2008 | 15 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Agonist-dependent internalization and trafficking of the human prostacyclin receptor: A direct role for Rab5a GTPase
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کلمات کلیدی
FBSCCVGFPHEKC-tailClathrin coated vesiclesRab5GPCRGRKAgonist - آگونیستHuman - انسانInternalization - داخلی سازیcarboxyl-terminal tail - دم کربوکسیل پایانیfoetal bovine serum - سرم جنین گاوHIP - مفصل ران یا مفصل هیپhemagglutinin - هماگلوتینینgreen fluorescent protein - پروتئین فلورسنت سبزprostacyclin - پروستاسیکلینhuman embryonic kidney - کلیه جنین انسانReceptor - گیرنده Prostacyclin receptor - گیرنده پروستات سیکلینG protein-coupled receptor - گیرندههای جفتشونده با پروتئین جی
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The human prostacyclin receptor (hIP) undergoes rapid agonist-induced internalization by largely unknown mechanism(s). Herein the involvement of Rab5 in regulating cicaprost-induced internalization of the hIP expressed in human embryonic kidney 293 cells was investigated. Over-expression of Rab5a significantly increased agonist-induced hIP internalization. Additionally, the hIP co-localized to Rab5a-containing endocytic vesicles in response to cicaprost stimulation and there was a coincident net translocation of Rab5 from the cytosol/soluble fraction of the cell. Co-immunoprecipitation studies confirmed a direct physical interaction between the hIP and Rab5a that was augmented by cicaprost. Whilst the dominant negative Rab5aS34N did not show decreased interaction with the hIP or fully impair internalization, it prevented hIP sorting to endocytic vesicles. Moreover, the GTPase deficient Rab5aQ79L significantly increased internalization and co-localized with the hIP in enlarged endocytic vesicles. While deletion of the carboxyl terminal (C)-tail domain of the hIP did not inhibit agonist-induced internalization, co-localization or co-immunoprecipitation with Rab5a per se, receptor trafficking was altered suggesting that it contains structural determinant(s) for hIP sorting post Rab5-mediated endocytosis. Taken together, data herein and in endothelial EA.hy 926 cells demonstrate a direct role for Rab5a in agonist-internalization and trafficking of the hIP and increases knowledge of the factors regulating prostacyclin signaling.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1783, Issue 10, October 2008, Pages 1914-1928
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1783, Issue 10, October 2008, Pages 1914-1928
نویسندگان
Martina B. O'Keeffe, Helen M. Reid, B. Therese Kinsella,