Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/30064
Title: MOLECULAR MECHANISMS FOR THE BIOGENESIS OF A PEROXISOME SUBCOMPARTMENT
Authors: LIU FANGFANG
Keywords: peroxisome, subcompartment, differentiation, protein sorting, positive feedback
Issue Date: 11-Jul-2011
Source: LIU FANGFANG (2011-07-11). MOLECULAR MECHANISMS FOR THE BIOGENESIS OF A PEROXISOME SUBCOMPARTMENT. ScholarBank@NUS Repository.
Abstract: Eukaryotic cells contain membrane-delimited organelles that execute specialized functions essential to cellular growth and metabolism. Organelles further diversify their function by differentiating into physically and functionally distinct subcompartments. For example, the ER is divided into distinct rough, smooth and transitional-ER. The mechanisms that generate organelle subcompartments are poorly understood. Peroxisomes are ubiquitous eukaryotic organelles that generally function in lipid metabolism, but also display a remarkable array of taxa-specific functions. Woronin bodies are specialized fungal peroxisomes that function to seal cell-cell channels when syncytial cellular filaments called hyphae are wounded. They are centered on a crystalline core of HEX and differentiate to become biochemically and functionally distinct sub-compartments. The aim of my thesis project is to use the Woronin body as a model system to study the generation and homeostasis of organelle sub-compartments. From a forward genetic screen for Woronin body loss-of-function, a PMP22 / MPV17-related membrane protein, WSC (Woronin Sorting Complex), was identified and shown to execute dual functions in Woronin body biogenesis. WSC specifically localizes to the membrane of Woronin body producing peroxisomes where it self-assembles into detergent-resistant oligomers that envelop HEX assemblies, forming asymmetrical nascent Woronin bodies. In a reaction requiring WSC, as well as a tethering protein called Leashin (LAH), these nascent organelles are delivered to the cell cortex, which permits their partitioning from mother peroxisomes and Woronin body inheritance. Despite using the canonical peroxisome import machinery for biogenesis, Woronin bodies are scarce compared to the overall peroxisome population. Using a photo-convertable peroxisome matrix marker, it is found that Woronin body producing peroxisomes differentiate to become enlarged and hyper-competent for matrix protein import. This process is controlled by HEX oligomers, which physically associates with the essential matrix import peroxin, PEX26, and promotes its enrichment in the membrane of differentiated peroxisomes. A PEX26 hypomorph disrupting differentiation produces increased numbers of aberrantly small Woronin bodies of reduced functionality. Taken together, these data suggest HEX and PEX26 comprise a positive feedback loop to promote peroxisome differentiation - HEX recruits PEX26, which in turn promotes the import of additional HEX and other matrix proteins. This regulates Woronin body abundance by producing a few dominant peroxisomes. The findings from this study show how a subpopulation of peroxisomes differentiates to produce the Woronin body subcompartments. HEX channels WSC to the membrane of Woronin body producing peroxisome, where it mediates Woronin body biogenesis through protein sorting; in a second function, HEX physically associates with PEX26 to promote peroxisome differentiation through positive feedback. This work shows how oligomers formed between proteins containing generic targeting signals and key components of organelle import machinery provide a basic mechanism for the production of organelle subpopulations of distinct composition and abundance.
URI: http://scholarbank.nus.edu.sg/handle/10635/30064
Appears in Collections:Ph.D Theses (Open)

Show full item record
Files in This Item:
File Description SizeFormatAccess SettingsVersion 
PhD thesis (LIU).pdf2.29 MBAdobe PDF

OPEN

NoneView/Download
Figures-part 1(LIU).pdf8.72 MBAdobe PDF

OPEN

NoneView/Download
Figures-part 2(LIU).pdf8.09 MBAdobe PDF

OPEN

NoneView/Download
Figurse-part 3(LIU).pdf7.81 MBAdobe PDF

OPEN

NoneView/Download
Figures-part 4(LIU).pdf8.96 MBAdobe PDF

OPEN

NoneView/Download

Page view(s)

135
checked on Dec 11, 2017

Download(s)

46
checked on Dec 11, 2017

Google ScholarTM

Check


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.