Analysis of the cell junction proteins CASK and claudin-5 in skeletal and cardiac muscle

Analysis of the cell junction proteins CASK and claudin-5 in skeletal and cardiac muscle

Bibliographic Details
Main Author: Sanford, Jamie Lynn
Language:English
Published: The Ohio State University / OhioLINK 2005
Subjects:
CASK
Claudin-5
Skeletal Muscle
Cardiac Muscle
Transgenic Mice
Cardiomyopathy
Neuromuscular Junction
Online Access:http://rave.ohiolink.edu/etdc/view?acc_num=osu1117553681
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spelling ndltd-OhioLink-oai-etd.ohiolink.edu-osu11175536812021-08-03T05:50:01Z Analysis of the cell junction proteins CASK and claudin-5 in skeletal and cardiac muscle Sanford, Jamie Lynn CASK Claudin-5 Skeletal Muscle Cardiac Muscle Transgenic Mice Cardiomyopathy Neuromuscular Junction In this dissertation, we examine the in vivo functions of two cell junction proteins, CASK and Claudin-5. CASK is a member of the membrane associated guanylate kinase family of proteins, while Claudin-5 is a protein that has been most thoroughly characterized as a component of tight junctions. This dissertation describes investigations of the CASK protein in skeletal muscle at the neuromuscular junction (NMJ) and Claudin-5 in cardiomyocytes We show that the CASK protein is present in skeletal muscle and is predominantly localized to the primary gutter of the NMJ, with a small amount of presynaptic localization. Immunoprecipitations reveal that CASK interacts in vivo with Dlg. We also examined the CASK protein in the C2C12 myogenic cell line and found that CASK localization is developmentally regulated and determined that CASK is recruited to the NMJ by a mechanism with is independent of that which recruits acetylcholine receptors. Finally, we generated two lines of transgenic mice, which overexpress a full-length or truncated version of the CASK protein. Overexpression of either the full-length or truncated CASK protein does not result in any morphological or functional abnormalities of the skeletal muscle or NMJ. However, overexpression of either CASK protein results in a loss of CASK protein presynaptically at the NMJ. Finally, overexpression of either CASK protein did not alter the expression or localization of Dlg. This dissertation also details an examination of the Claudin-5 protein in cardiac muscle from wild-type mice and two mouse models of cardiomyopathy, the mdx and dko mouse. We show that the Claudin-5 protein is present in normal cardiac muscle and is localized to the lateral membranes of cardiomyocytes. We also demonstrate that Claudin-5 protein expression and localization is unaltered in hearts from mdx mice, but is downregulated in dko hearts, as compared to normal hearts. Expression levels of cell junction proteins present at the intercalated disc were unaltered in hearts of dko mice. Furthermore, the lateral membranes of dko mice exhibit an abnormal wavy appearance. These experiments demonstrated that the cardiomyopathy of dko mice is associated with a breakdown of the lateral membranes of cardiomyocytes. 2005-07-14 English text The Ohio State University / OhioLINK http://rave.ohiolink.edu/etdc/view?acc_num=osu1117553681 http://rave.ohiolink.edu/etdc/view?acc_num=osu1117553681 unrestricted This thesis or dissertation is protected by copyright: all rights reserved. It may not be copied or redistributed beyond the terms of applicable copyright laws.
collection NDLTD
language English
sources NDLTD
topic CASK
Claudin-5
Skeletal Muscle
Cardiac Muscle
Transgenic Mice
Cardiomyopathy
Neuromuscular Junction
spellingShingle CASK
Claudin-5
Skeletal Muscle
Cardiac Muscle
Transgenic Mice
Cardiomyopathy
Neuromuscular Junction
Sanford, Jamie Lynn
Analysis of the cell junction proteins CASK and claudin-5 in skeletal and cardiac muscle
author Sanford, Jamie Lynn
author_facet Sanford, Jamie Lynn
author_sort Sanford, Jamie Lynn
title Analysis of the cell junction proteins CASK and claudin-5 in skeletal and cardiac muscle
title_short Analysis of the cell junction proteins CASK and claudin-5 in skeletal and cardiac muscle
title_full Analysis of the cell junction proteins CASK and claudin-5 in skeletal and cardiac muscle
title_fullStr Analysis of the cell junction proteins CASK and claudin-5 in skeletal and cardiac muscle
title_full_unstemmed Analysis of the cell junction proteins CASK and claudin-5 in skeletal and cardiac muscle
title_sort analysis of the cell junction proteins cask and claudin-5 in skeletal and cardiac muscle
publisher The Ohio State University / OhioLINK
publishDate 2005
url http://rave.ohiolink.edu/etdc/view?acc_num=osu1117553681
work_keys_str_mv AT sanfordjamielynn analysisofthecelljunctionproteinscaskandclaudin5inskeletalandcardiacmuscle
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