TROPOMYOSINS IN NORMAL AND TRANSFORMED CELLS

Project Details

Description

This proposal is aimed at understanding the molecular functions of
the multiple isoforms of tropomyosin in the reorganization of
microfilaments following oncogenic transformation of cultured
cells. We have demonstrated that tropomyosins with high Mr values
are replaced with tropomyosins with low Mr values concomitant with
the morphological alterations associated with a variety of cultured
rat cell transformations. Furthermore, we have found two new
actin-bundling proteins control the binding of the low Mr
tropomyosins, and see how changes in tropomyosin-binding regulate
the assembly of microfilaments upon cell transformation. Using
limited proteolysis we plan to dissect the actin-bundling proteins,
as well as those of the tropomyosins. We will microinject the two
new actin-bundling proteins, high and low Mr tropomyosins, and the
monoclonal antibodies, into living cells to see if the two actin-
bundling proteins stimulate or inhibit the binding of low Mr
tropomyosins to the actin bundles of stress fibers, and to
determine if changes in tropomyosin-binding alter the organization
of microfilaments and microtubules. Finally, we propose to
undertake an in depth analysis of the structures and molecular
compasitions of microfilaments and microtubules to determine if
they change upon cell transformation. We will examine if such
changes are functionally related to the changes in tropomyosin
patterns. Our long-term goal is to understand how differential
expression of tropomyosin effects changes in cell morphology, and
why it is a very sensitive indicator of the transformed phenotype.
StatusFinished
Effective start/end date9/1/888/31/93

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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