Hello my name is Jonathan Soboloff and
today I'm going to talk a little bit
about some recent work performed in
my lab, investigating mechanisms
regulating STIM expression and
function in calcium signaling.
Before getting too far
into my current research,
I'd like to talk a little about the
physiological roles of calcium signals.
Calcium signals control a wide variety
of distinct physiological events.
Whereas calcium signals themselves
typically occur quite rapidly in a time
frame of seconds to minutes,
the physiological consequences of these
signals can last over
a much longer time period.
Some of the immediate effects of calcium
signals can be detected immediately
over a time frame,
similar to the calcium signal itself.
For example, muscle contraction, changes
in the metabolic state of certain enzymes,
or membrane fusion, such as for
example in secretion.
Other calcium signals occur
over a much longer time frame,
really long after the calcium
signal has already ended,
such as changes in gene expression,
changes in cell proliferation, or
changes in apoptosis (otherwise
known as cell death).
The major goal of my lab is to understand
this link between short-term changes
in calcium signals and these
longer-term changes in cell function.
Now I'd like to talk a little about
receptor-mediated control of calcium
At rest, the concentration of
calcium in the cytosol is many-fold
lower than outside of the cell or
in the lumen of the.
This difference is maintained by
the combined action of the plasma
membrane calcium ATPase (PMCA) and
the sarco/endoplasmic reticulum
calcium ATPase (SERCA).
When a ligand binds to a PLC
(phospholipase C-coupled receptor),
it initiates a series of events leading
to elevation of cytosol calcium
The first step in this process is
breakdown of phosphatidyl inositol (PIP2)
into two bio-active metabolites,
diacylglycerol (DAG) and IP3.
DAG has a number of different targets,
one of which is receptor-operated calcium
channels (ROCs), which upon binding
of diacylglycerol permit the entry of
calcium into the cytosol from
the extracellular space.
IP3 binds to its receptor on the Membrane,
causing the movement of calcium
out of the Lumen and into the cytoplasm,
and this movement of calcium out
of the Lumen tends to cause
a depletion of Calcium concentration.
This Calcium depletion leads to the
activation of a separate class of calcium
channels, termed store-operated
calcium channels (SOCs).
Because both SOCs and ROCs are activated
downstream of receptors at least
physiologically, there's been a great
deal of confusion over the years over
whether a channel is receptor-operated or
Much of this confusion was
addressed in 2005 and 2006,
with the identification of
the molecular mediators of SOC and
it's these proteins that have been
the focus of my research since that time.