Please use this identifier to cite or link to this item: https://hdl.handle.net/20.500.12202/956
Title: Intracellular targeting and functions of AKAP220
Authors: Li, Dongying
Keywords: Cellular biology.
Issue Date: 2008
Publisher: ProQuest Dissertations & Theses
Citation: Source: Dissertation Abstracts International, Volume: 69-03, Section: B, page: 1415.;Advisors: Charles Rubin.
Abstract: In this thesis, we demonstrate that AKAP220, as first intermediate filament associating AKAP, is a binding partner for vimentin filaments. By immunofluorescence staining, co-immunoprecipitation and electron microscopy, we showed AKAP220 tightly bound with vimentin filaments. AKAP220 associates with vimentin intermediate filaments via two binding sites. The independent N- and C-terminal binding domains of AKAP220 can simultaneously engage two vimentin molecules thereby cross-linking intermediate filaments. AKAP220 mediated cross-linking is consistent with effects of the anchor protein on intermediate filament architecture. AKAP220 markedly alters vimentin organization at specific intracellular sites. Depletion of AKAP220 caused decompression and expansion of vimentin filaments. Overexpression of AKAP220 promoted vimentin filament condensation, concentration and shortening. AKAP220 may play an important role in triggering regulated cell death. Treatment of cells with BFA disrupts Golgi structure and causes aggregation of vimentin filaments, which induces cytotoxicity and apoptosis. Loss of AKAP220 imparted a high level of resistance to BFA-induced cytotoxicity, suggesting that the anchor protein plays a role in mediating the BFA-induced death response. During mitosis, AKAP220 may mediate phosphorylation of vimentin at Ser38 by PKA. These data shed light on study on structure regulations and functions of intermediate filaments.
URI: https://ezproxy.yu.edu/login?url=http://gateway.proquest.com/openurl?url_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&res_dat=xri:pqm&rft_dat=xri:pqdiss:3303364
https://hdl.handle.net/20.500.12202/956
Appears in Collections:Albert Einstein College of Medicine: Doctoral Dissertations

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