자료유형  

 학위논문

Control Number  

0017164457

International Standard Book Number  

9798384043737

Dewey Decimal Classification Number  

574

Main Entry-Personal Name  

Pletan, Madison Lynn.

Publication, Distribution, etc. (Imprint  

[S.l.] : University of Michigan., 2024

Publication, Distribution, etc. (Imprint  

Ann Arbor : ProQuest Dissertations & Theses, 2024

Physical Description  

107 p.

General Note  

Source: Dissertations Abstracts International, Volume: 86-03, Section: B.

General Note  

Advisor: Tsai, Billy.

Dissertation Note  

Thesis (Ph.D.)--University of Michigan, 2024.

Summary, Etc.  

요약The endoplasmic reticulum (ER) is a dynamic network of membranous sheets and tubules that extends throughout the cell body and acts as a hub for protein synthesis and folding, protein quality control, phospholipid and steroid biosynthesis, calcium homeostasis, and organelle biogenesis, among other functions. To accomplish this wide range of functions, the ER exhibits remarkable structural diversity. Its continuous membrane is constantly shaped and remodeled by various morphogenic proteins, including reticulons (curvature-inducing proteins that support tubule formation), atlastins (fusogenic proteins that bring opposing tubules together), and lunapark (membrane proteins that stabilize the resulting tubular junctions). This dissertation examines two unexpected functions of the ER junctional sites: 1) as quality control storage sites for mislocalized nuclear proteins, and 2) as penetration sites for a nonenveloped virus. The nuclear pore complex (NPC) is the large, modular channel mediating all cargo transport in and out of the nucleus; it is composed of 30 individual nucleoporins (Nups) assembled in strict stoichiometries. Mislocalization of Nups to the cytoplasm has been observed in many neurodegenerative diseases and some cancers, but the cellular response to this phenomenon is unclear. In this research, we describe a model system of Nup mislocalization and identify a discrete storage site at the ER membrane where excess Nups are routed (with the activity of the kinesin-1 motor and several ER morphogenic proteins). Furthermore, we show that the storage site sequesters Nups from re-localizing at the nuclear envelope and disrupting nucleo-cytoplasmic transport. Thus, this ER junctional site serves a quality control function for nuclear pore proteins. The second portion of this dissertation focuses on how ER junctions are exploited by a different large, proteinaceous cargo: SV40 polyomavirus virions. On their journey to the nucleus for replication, SV40 particles transit through the ER lumen, where they undergo a series of conformational changes to prepare them to penetrate the ER membrane at "foci" sites. Subsequently, the virus escapes into the cytosol and enters the nucleus to cause infection. Here we show that two prominent ER fusogenic proteins, ATL2 and ATL3, play critical, yet distinct roles in facilitating SV40 membrane penetration. ATL3 mobilizes to the virus-induced ER foci, where it engages an SV40-containing membrane penetration complex and promotes fusion of ER tubules via its GTPase activity. ATL2 does not mobilize to the foci or directly engage the virus; rather, it supports the reticulated ER morphology more broadly, allowing ATL3 to interact with the morphogenic complex. These findings show how a virus can hijack the ER-morphogenic activity of host proteins, reshaping the ER architecture to carry out its replication cycle. Together, the chapters of this dissertation highlight how the basic junctional structure of the ER can support two disparate cellular processes: storage of mislocalized nucleoporins and membrane penetration of a nonenveloped virus. In both cases, the ER-morphogenic machinery enables the ER membrane to harbor large, proteinaceous particles at distinct perinuclear depots.

Subject Added Entry-Topical Term  

Cellular biology.

Subject Added Entry-Topical Term  

Molecular biology.

Subject Added Entry-Topical Term  

Virology.

Subject Added Entry-Topical Term  

Biochemistry.

Index Term-Uncontrolled  

Endoplasmic reticulum

Index Term-Uncontrolled  

Protein quality control

Index Term-Uncontrolled  

Polyomavirus

Index Term-Uncontrolled  

Nuclear pore complex

Index Term-Uncontrolled  

Virus host interactions

Added Entry-Corporate Name  

University of Michigan Cellular & Molecular Biology

Host Item Entry  

Dissertations Abstracts International. 86-03B.

Electronic Location and Access  

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Control Number  

joongbu:654009