رکورد قبلیرکورد بعدی

" The interconnected network of ESCRT and non-ESCRT cellular proteins required for retroviral release "


Document Type : Latin Dissertation
Language of Document : English
Record Number : 52869
Doc. No : TL22823
Call number : ‭3340122‬
Main Entry : Gisselle Nilda Medina
Title & Author : The interconnected network of ESCRT and non-ESCRT cellular proteins required for retroviral release\ Gisselle Nilda Medina
College : State University of New York at Stony Brook
Date : 2008
Degree : Ph.D.
student score : 2008
Page No : 147
Abstract : The structural polyprotein, Gag, drives the assembly and release of retroviruses from the plasma membrane of cells and its expression alone is sufficient for the formation of virus-like particles (VLPs). Trafficking and membrane targeting of Gag requires a series of events that are directed by the interaction between cellular proteins and regions in Gag known as L domains, however the precise mechanism is not well understood. The functionally exchangeable L domains in the Gag protein of the human retrovirus, HIV-1, and the related avian retrovirus, ASV, bind Tsg101 and Nedd4, respectively. Tsg101 and Nedd4 function in endocytic sorting and trafficking of cargo proteins typically destined for degradation. In the first part of my thesis, I determined if the cellular factors were functionally exchangeable as a means of determining whether HIV and ASV use the same trafficking pathway. The results obtained by using dominant negative forms of Tsg101, Nedd4, and Vps4, an ATPase that regulates their availability, suggest that HIV-1 and ASV use different pathways, even though they both utilize the endocytic machinery. In particular, covalently linking Tsg101 to an ASV Gag L domain mutant ablated the requirement for Nedd4 for Gag release, but budding occurred through a different membrane region. The second part of my thesis examines the involvement of non-endocytic factors such as Sprouty2, in the release of HIV-1 Gag. Spry2 modulates ESCRT-mediated trafficking pathways of EGFR and requires binding to phosphatidylinositol 4,5-biphosphate [ PI(4,5)P 2 ] to exert its function. In this study, I found that depletion of endogenous Spry2 inhibited VLP production as did expression of a C-terminal fragment of the Spry2 protein, specifically by sequestering Gag into intracellular vesicles. Furthermore, a Spry2 mutant lacking the only conserved sequences in the N-terminal domain relieved the inhibitory effects. Interestingly, a mutant of Spry2 that had no detectable effect on WT Gag release promoted release of a Gag mutant lacking a functional Tsg101 binding site. Examination of cells by confocal microscopy revealed that wild type-Spry2 co-localized with PI(4,5)P 2 in complexes that were resistant to cold Triton X-100 extraction. In contrast, the Spry2 variant failed to co-localized with PI(4,5)P2 .
Subject : Biological sciences; Retroviruses; HIV-1; Cellular proteins; Virus budding; Endocytic pathway; Gag protein; Cellular biology; Microbiology; Virology; 0720:Virology; 0410:Microbiology; 0379:Cellular biology
Added Entry : State University of New York at Stony Brook
کپی لینک

پیشنهاد خرید
پیوستها
عنوان :
نام فایل :
نوع عام محتوا :
نوع ماده :
فرمت :
سایز :
عرض :
طول :
3340122_9396.pdf
3340122.pdf
پایان نامه لاتین
متن
application/octet-stream
10.16 MB
85
85
نظرسنجی
نظرسنجی منابع دیجیتال

1 - آیا از کیفیت منابع دیجیتال راضی هستید؟