NOVEL T CELL ACTIVATION GENE IN DEVELOPING NEURONS

Project: Research project

Project Details

Description

DESCRIPTION (Adapted from applicant's abstract): Mental effects on physical
health are mediated by interactions between the nervous and immune systems.
These systems are coordinately regulated through common molecules. Given
the common expression of cell surface receptors and soluble mediators in
both systems, one might expect to find intracellular proteins that are
common to both systems and may be involved in signaling. The investigators
isolated a cDNA sequence from a cDNA library prepared from IL2-stimulated,
cloned T lymphocytes which has recently been identified as the KvBeta2
subunit of voltage-gated K channels. Potassium channels maintain membrane
potential and determine the excitability of cells. Beta subunits appear to
regulate the conductance properties of K channels. KvBeta2 is expressed in
proliferating lymphocytes and postnatal neurons. The hypothesis proposed is
that Beta subunit expression affects lymphocyte and neuronal function
through modulation of K channel conductance. The first aim will test the
hypothesis that Beta subunit expression is required for IL2-driven T cell
proliferation. The investigators indicate that with their knowledge of IL-2
induced gene expression, the precise point at which cell cycle progression
is inhibited will be determined. In a second aim, studies will be initiated
to define cis elements in a Beta subunit promoter and corresponding DNA
binding proteins which are responsible for IL2-induced Beta subunit
expression in lymphocytes. In a third aim, activation-dependent
phosphorylation sites on Beta subunits will be determined in vitro and in
vivo. Once specific phosphoamino acids are found, mutant proteins
precluding specific phosphorylation will be prepared to determine the
requirement of phosphorylation for Beta subunit function during IL2-driven
proliferation. To determine if Beta subunit is required for lymphocytic and
neuronal development and function, mice homozygous for a Beta subunit null
allele will be prepared. While these animals may be immunodeficient at
birth, the effect of Beta subunit deletion on neuronal development should
not appear until postnatal neuronal maturation occurs. These studies will
define the functional significance for KvBeta subunits in both the nervous
and immune systems and begin to address molecular mechanisms regulating
tissue specific expression.
StatusFinished
Effective start/end date7/1/966/30/00

ASJC

  • Genetics
  • Molecular Biology
  • Immunology

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