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

Record Type:	Language materials, manuscript : Monograph/item
Title/Author:	Application of BioID to Identify Novel Nuclear Envelope Constituents and Functions./
Author:	KC, Birendra.
Description:	1 online resource (152 pages)
Notes:	Source: Dissertations Abstracts International, Volume: 79-12, Section: B.
Contained By:	Dissertations Abstracts International79-12B.
Subject:	Molecular biology. -
Online resource:	click for full text (PQDT)
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. - 1 online resource (152 pages)

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

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

Includes bibliographical references

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.

Electronic reproduction.
Ann Arbor, Mich. :
ProQuest,
2024

Mode of access: World Wide Web

ISBN: 9780438076280Subjects--Topical Terms:

583443
Molecular biology.
Subjects--Index Terms:

BAFIndex Terms--Genre/Form:

554714
Electronic books.

Application of BioID to Identify Novel Nuclear Envelope Constituents and Functions.
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502 $a Thesis (Ph.D.)--University of South Dakota, 2017.
504 $a Includes bibliographical references
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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