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Application of BioID to Identify Nov...

KC, Birendra.

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Application of BioID to Identify Novel Nuclear Envelope Constituents and Functions.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	Application of BioID to Identify Novel Nuclear Envelope Constituents and Functions./
作者:	KC, Birendra.
出版者:	Ann Arbor : ProQuest Dissertations & Theses, : 2017,
面頁冊數:	152 p.
附註:	Source: Dissertations Abstracts International, Volume: 79-12, Section: B.
Contained By:	Dissertations Abstracts International79-12B.
標題:	Molecular biology. -
電子資源:	https://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=10681415
ISBN:	9780438076280

Application of BioID to Identify Novel Nuclear Envelope Constituents and Functions.
KC, Birendra.

Application of BioID to Identify Novel Nuclear Envelope Constituents and Functions. - Ann Arbor : ProQuest Dissertations & Theses, 2017 - 152 p.

Source: Dissertations Abstracts International, Volume: 79-12, Section: B.

Thesis (Ph.D.)--University of South Dakota, 2017.

.

The nuclear envelope (NE) is a highly specialized extension of the endoplasmic reticulum crucial for diverse cellular roles including organization of peripheral heterochromatin, separation of the nuclear and cytoplasmic compartments, and nuclear positioning via mechanical linkages with the cytoskeleton. Not surprisingly, the mutations in NE constituents are associated with several rare human diseases. Identification of NE constituents and their function in health and disease is key to uncovering the underlying mechanisms of NE-associated diseases. We utilized the second-generation of proximity-dependent biotinylation (BioID2) to map the constituency of the inner nuclear membrane and identified a lamin-associated transmembrane kinase called VRK2A. We show that VRK2A phosphorylates and subtly alters the nuclear mobility of barrier to autointegration factor (BAF), a small dynamic DNA-binding protein with roles including cell division and NE assembly. Besides residing in the NE and nucleoplasm, BAF also exists in the cytosol where it binds DNA. We observed that VRK2A co-localizes with BAF at induced cytosolic DNA foci. VRK2 depletion significantly increases the number of these cytosolic DNA foci. We observed that BAF and VRK2 regulate interferon production via a DNA-sensing mechanism of the innate immune system, and that this signaling depends on BAF and is enhanced by the loss of VRK2. Our working model proposes that BAF enables cytosolic DNA to elicit a robust innate immune response and VRK2A negatively regulates this activity of BAF. The results presented in this dissertation unveil a new member of the inner nuclear membrane and provide evidence for the role of the NE in innate immunity.

ISBN: 9780438076280Subjects--Topical Terms:

517296
Molecular biology.
Subjects--Index Terms:

BAF

Application of BioID to Identify Novel Nuclear Envelope Constituents and Functions.
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500 $a Publisher info.: Dissertation/Thesis.
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506 $a .
520 $a The nuclear envelope (NE) is a highly specialized extension of the endoplasmic reticulum crucial for diverse cellular roles including organization of peripheral heterochromatin, separation of the nuclear and cytoplasmic compartments, and nuclear positioning via mechanical linkages with the cytoskeleton. Not surprisingly, the mutations in NE constituents are associated with several rare human diseases. Identification of NE constituents and their function in health and disease is key to uncovering the underlying mechanisms of NE-associated diseases. We utilized the second-generation of proximity-dependent biotinylation (BioID2) to map the constituency of the inner nuclear membrane and identified a lamin-associated transmembrane kinase called VRK2A. We show that VRK2A phosphorylates and subtly alters the nuclear mobility of barrier to autointegration factor (BAF), a small dynamic DNA-binding protein with roles including cell division and NE assembly. Besides residing in the NE and nucleoplasm, BAF also exists in the cytosol where it binds DNA. We observed that VRK2A co-localizes with BAF at induced cytosolic DNA foci. VRK2 depletion significantly increases the number of these cytosolic DNA foci. We observed that BAF and VRK2 regulate interferon production via a DNA-sensing mechanism of the innate immune system, and that this signaling depends on BAF and is enhanced by the loss of VRK2. Our working model proposes that BAF enables cytosolic DNA to elicit a robust innate immune response and VRK2A negatively regulates this activity of BAF. The results presented in this dissertation unveil a new member of the inner nuclear membrane and provide evidence for the role of the NE in innate immunity.
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650 4 $a Cellular biology. $3 3172791
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