Abstract/Details

Functional analysis of Hic-5/ARA55 isoforms in C2C12 myogenesis


2006 2006

Other formats: Order a copy

Abstract (summary)

Hic-5 is a focal adhesion protein of paxillin superfamily that was initially cloned from mouse osteoblasts as a TGF-β or H2O2 inducible cDNA. As well, Hic-5 was independently identified as an Androgen receptor activator (ARA55). Conflicting data have implicated Hic-5 in opposing processes. With two Hic-5 isoforms documented, I hypothesized that multiple Hic-5 isoforms may exist that have both overlapping and isoform-specific functions, which may explain those discrepancies. To test this hypothesis, I have utilized C2C12 myoblasts and analyzed the roles of Hic-5 isoforms in development and homeostasis.

1. I have confirmed the presence of the two previous reported Hic-5 isoforms (α and β) and uncovered 10 additional novel Hic-5 transcripts. Conceptually translated proteins from these transcripts significantly differ at the N-terminal region and likely have distinct binding properties and functions. Hic-5 isoforms have distinct tissue distribution and are developmentally regulated in the mouse mammary gland in vivo (Chapter two).

2. I found that: (a) myoblasts express multiple Hic-5 isoforms; (b) the two predominant isoforms, Hic-5α and Hic-5β, are differentially expressed during myogenesis; (c) any experimentally-induced change in Hic-5 expression results in a substantial increase in apoptosis during differentiation; (d) ectopic expression of Hic-5α is permissive to differentiation while expression of either Hic-5β or antisense Hic-5 reduces myoblast chemo-differentiation and blocks fusion; (e) Hic-5 localizes to focal adhesion in C2C12 myoblasts and perturbation of Hic-5 leads to defects in cell spreading; (f) perturbations of Hic-5 expression interfere with the normal expression dynamics of laminin; and (g) the rescue of myoblast survival and differentiation by laminin but not fibronectin suggests that Hic-5 isoforms differentially regulate myogenesis due to their different impacts on cell-ECM interaction, focal adhesion dynamics and integrin signaling (Chapter Three).

In summary, the roles Hic-5 may assume in development and homeostasis are complex and the different Hic-5 isoforms may mediate distinct physiological and/or pathological responses in cells. Therefore, a more precise analysis of Hic-5 isoforms is required to more fully understand the roles of not only Hic-5, but also integrin signaling in normal and diseased cells ( Chapter four and five).

Indexing (details)


Subject
Cellular biology
Classification
0379: Cellular biology
Identifier / keyword
Biological sciences; ARA55; Hic-5/ARA55; Isoforms; Myogenesis
Title
Functional analysis of Hic-5/ARA55 isoforms in C2C12 myogenesis
Author
Gao, Zhengliang
Number of pages
137
Publication year
2006
Degree date
2006
School code
0118
Source
DAI-B 67/11, Dissertation Abstracts International
Place of publication
Ann Arbor
Country of publication
United States
ISBN
9780542977206
Advisor
Schwartz, Lawrence M.
University/institution
University of Massachusetts Amherst
University location
United States -- Massachusetts
Degree
Ph.D.
Source type
Dissertations & Theses
Language
English
Document type
Dissertation/Thesis
Dissertation/thesis number
3242316
ProQuest document ID
305303853
Copyright
Database copyright ProQuest LLC; ProQuest does not claim copyright in the individual underlying works.
Document URL
http://search.proquest.com/docview/305303853
Access the complete full text

You can get the full text of this document if it is part of your institution's ProQuest subscription.

Try one of the following:

  • Connect to ProQuest through your library network and search for the document from there.
  • Request the document from your library.
  • Go to the ProQuest login page and enter a ProQuest or My Research username / password.