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The endoplasmic reticulum diffusion barrier and inter-organelle contact sites Chao, Jesse Tzu-Cheng
Abstract
Polarization of cellular membranes into domains is an important mechanism to compartmentalize cellular activities within the membrane and establish cell polarity. Recent studies have uncovered that the endoplasmic reticulum (ER) is polarized by diffusion barriers, which in neurons controls glutamate signaling in dendritic spines, but the molecular identity of these diffusion barriers is unknown. In Chapter 2 we show that a direct interaction between integral ER protein Scs2 and septin Shs1 creates the ER diffusion barrier in yeast. We uncovered a new ER-associated polarisome subunit, Epo1, which is required for the tethering of ER to septins. The human homologue of Scs2, VAP-B, also interacts with Shs1 in yeast indicating that the tether may be conserved. As mutations in VAP-B cause amyotrophic lateral sclerosis, loss of ER polarization in dendritic spines is a potential mechanism underlying motorneuron disease. Synthesis of phospholipids, sterols and sphingolipids is thought to occur at contact sites between the ER and other organelles because many lipid synthesizing enzymes are enriched at contact sites. In only a few cases have the enzymes been localized to contacts in vivo and in no instances have the contacts been demonstrated to be required for enzyme function. In Chapter 3 we show that plasma membrane (PM) - endoplasmic reticulum (ER) contact sites in yeast are required for phosphatidylcholine synthesis and regulate the activity of a key enzyme, Opi3, whose activity requires a lipid binding protein, Osh3. Thus, membrane contact sites provide a structural mechanism to regulate lipid synthesis.
Item Metadata
Title |
The endoplasmic reticulum diffusion barrier and inter-organelle contact sites
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2013
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Description |
Polarization of cellular membranes into domains is an important mechanism to
compartmentalize cellular activities within the membrane and establish cell polarity.
Recent studies have uncovered that the endoplasmic reticulum (ER) is polarized by
diffusion barriers, which in neurons controls glutamate signaling in dendritic spines, but
the molecular identity of these diffusion barriers is unknown. In Chapter 2 we show that
a direct interaction between integral ER protein Scs2 and septin Shs1 creates the ER
diffusion barrier in yeast. We uncovered a new ER-associated polarisome subunit,
Epo1, which is required for the tethering of ER to septins. The human homologue of
Scs2, VAP-B, also interacts with Shs1 in yeast indicating that the tether may be
conserved. As mutations in VAP-B cause amyotrophic lateral sclerosis, loss of ER
polarization in dendritic spines is a potential mechanism underlying motorneuron
disease.
Synthesis of phospholipids, sterols and sphingolipids is thought to occur at
contact sites between the ER and other organelles because many lipid synthesizing
enzymes are enriched at contact sites. In only a few cases have the enzymes been
localized to contacts in vivo and in no instances have the contacts been demonstrated
to be required for enzyme function. In Chapter 3 we show that plasma membrane (PM) -
endoplasmic reticulum (ER) contact sites in yeast are required for phosphatidylcholine
synthesis and regulate the activity of a key enzyme, Opi3, whose activity requires a lipid
binding protein, Osh3. Thus, membrane contact sites provide a structural mechanism to
regulate lipid synthesis.
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Genre | |
Type | |
Language |
eng
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Date Available |
2014-10-31
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Provider |
Vancouver : University of British Columbia Library
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Rights |
Attribution-NonCommercial-NoDerivs 2.5 Canada
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DOI |
10.14288/1.0103365
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Graduation Date |
2013-11
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Campus | |
Scholarly Level |
Graduate
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Rights URI | |
Aggregated Source Repository |
DSpace
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Rights
Attribution-NonCommercial-NoDerivs 2.5 Canada