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Implications of alpha-dystroglycan glycosylation in the proper assembly of the dystroglycan associated protein complex and the polarized distribution of the inwardly rectifying potassium channel, Kir4.1, and the water permeable channel, AQP4, in perivascular glia Rurak, Jennifer Mary Elizabeth
Abstract
The dystroglycan protein complex spans the plasma membrane and provides a link between the cytoskeleton and the extracellular matrix (ECM). Defective O-linked glycosylation of α-dystroglycan (α-DG) within the complex severs this link leading to a subset of muscular dystrophies known as the dystroglycanopathies. These are characterized by muscle weakness and degeneration as well as by brain and ocular defects of unknown etiology. In brain and retina, α-DG and ECM molecules are enriched at astrocytic domains abutting blood vessels where they may be involved in localizing the inwardly rectifying potassium channel, Kir4.1, and aquaporin channel, AQP4, to astrocytic endfeet. To investigate the role of ECM ligand-binding to glycosylated sites on α-DG in the polarized distribution of these channels in vivo, we used the Large [superscript] myd mouse, an accepted animal model for dystroglycanopathies. We found that Kir4.1 and AQP4 are lost from astrocytic endfeet in brain while significant labeling for these channels is still detected at analogous cell domains in retina. Furthermore, while both α- and β₁- syntrophins are lost from perivascular astrocytes in brain of the Large [superscript] myd mouse, labeling for β₁-syntrophin is still evident at parallel domains in retina. These findings show that while ligand-binding to glycosylated sites on α-DG in concert with α- and β₁-syntrophins is crucial for the polarized distribution of Kir4.1 and AQP4 to functional domains in brain, distinct mechanisms may contribute to their localization in retina.
Item Metadata
Title |
Implications of alpha-dystroglycan glycosylation in the proper assembly of the dystroglycan associated protein complex and the polarized distribution of the inwardly rectifying potassium channel, Kir4.1, and the water permeable channel, AQP4, in perivascular glia
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Creator | |
Publisher |
University of British Columbia
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Date Issued |
2007
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Description |
The dystroglycan protein complex spans the plasma membrane and provides a link
between the cytoskeleton and the extracellular matrix (ECM). Defective O-linked
glycosylation of α-dystroglycan (α-DG) within the complex severs this link leading to a
subset of muscular dystrophies known as the dystroglycanopathies. These are
characterized by muscle weakness and degeneration as well as by brain and ocular
defects of unknown etiology. In brain and retina, α-DG and ECM molecules are enriched
at astrocytic domains abutting blood vessels where they may be involved in localizing the
inwardly rectifying potassium channel, Kir4.1, and aquaporin channel, AQP4, to
astrocytic endfeet. To investigate the role of ECM ligand-binding to glycosylated sites on
α-DG in the polarized distribution of these channels in vivo, we used the Large [superscript] myd mouse,
an accepted animal model for dystroglycanopathies. We found that Kir4.1 and AQP4 are
lost from astrocytic endfeet in brain while significant labeling for these channels is still
detected at analogous cell domains in retina. Furthermore, while both α- and β₁-
syntrophins are lost from perivascular astrocytes in brain of the Large [superscript] myd mouse, labeling
for β₁-syntrophin is still evident at parallel domains in retina. These findings show that
while ligand-binding to glycosylated sites on α-DG in concert with α- and β₁-syntrophins
is crucial for the polarized distribution of Kir4.1 and AQP4 to functional domains in
brain, distinct mechanisms may contribute to their localization in retina.
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Genre | |
Type | |
Language |
eng
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Date Available |
2011-03-10
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Provider |
Vancouver : University of British Columbia Library
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Rights |
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.
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DOI |
10.14288/1.0302194
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URI | |
Degree | |
Program | |
Affiliation | |
Degree Grantor |
University of British Columbia
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Campus | |
Scholarly Level |
Graduate
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Aggregated Source Repository |
DSpace
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Rights
For non-commercial purposes only, such as research, private study and education. Additional conditions apply, see Terms of Use https://open.library.ubc.ca/terms_of_use.