|
Research Interest: 
Calcium Signaling in Muscle Physiology and
Tumorigenesis
Description of Research Activity:
Ion calcium, as a second messenger, plays an
essential role in many cell processes including
muscle contraction, cell proliferation and
apoptosis. My laboratory’s research interests
focus on Ca2+ signaling in muscle
physiology and tumorigenesis. Particularly, we
study Store-Operated Ca2+ Entry (SOCE),
a pathway to allow extracellular Ca2+
to pass the plasma membrane for replenishment of
the depleted intracellular Ca2+
stores.
With several muscle specific proteins deficient
mouse strains, we previously demonstrated that SOCE
exists in skeletal muscle with important
physiological functions. The activation of SOCE
requires the adjacency of plasma membrane and
sarcoplasmic reticulum (SR) membrane, the
interaction between the Ca2+ sensor
docking at ER/SR and the Ca2+ channel
locating at plasma membrane, as well as the presence
of ryanodine receptor. Using microarray and RNA
interfering techniques, we have identified
co-factors for regulation of SOCE in muscles. Our
current effort is to characterize the role of these
genes in SOCE and to investigate their functions in
muscle fatigue, muscle development and aging.
Alteration in SOCE not only causes muscle
weakness but may also contribute to carcinogenesis,
such as in prostate cancer and esophageal tumor
cells. We have found that several key proteins in
SOCE pathway are either down-regulated or
up-regulated in those cancer cells. Our research
here is to understand the molecular mechanisms
underlying the perturbed Ca2+ signaling
and how the changes in SOCE affects cancer cell
growth, migration and apoptosis.
The long-term goal of our research is to identify
therapeutic targets to overcome muscle weakness in
aged population or to reduce tumorigenesis in cancer
patients. The experimental methods to accomplish our
aims include molecular biology techniques and
heterogeneous expression of eukaryotic genes,
spectrofluorometer measurement of intracellular Ca2+
and confocal microscopy live cell imaging of Ca2+
and fluorescent protein-tagged molecules.
Selected Recent publications:
Pan Z, Damron D, Nieminen AL, Bhat MB,
Ma J. Depletion of Intracellular Ca2+ by
Caffeine and Ryanodine Induces Apoptosis of Chinese
Hamster Ovary Cells Transfected with Ryanodine
Receptor. J. Biol. Chem. 2000;
275(26): 19978-19984
Pan Z, Bhat MB, Nieminen AL, Ma J.
Synergistic movements of Ca2+ and Bax in
cells undergoing apoptosis. J. Biol. Chem.
2001; 276: 32257-32263
Yang D, Pan Z, Takeshima H, Wu C, Nagaraj
RY, Ma J, Cheng H. RyR3 amplifies RyR1-mediated Ca2+-induced
Ca2+ release in neonatal mammalian
skeletal muscle. J. Biol. Chem. 2001;
276: 40210-40214
Pan Z, Yang D, Nagaraj RY, Nosek TA, Nishi
M, Takeshima H, Cheng H, Ma J. Deletion of mg29 Gene
Leads to Defective Function of Store-Operated Ca2+
Channel in Skeletal Muscle. Nature Cell
Biology. 2002; 4(5) 379-383
Shin DW, Pan Z, Kim EK, Lee JM, Bhat MB,
Parness J, Kim DH, Ma J. A Retrograde Signal from
Calsequestrin for the Regulation of Store-operated
Ca2+ Entry in Skeletal Muscle. J.
Biol. Chem. 2003, 278: (5): 3286-3292
Ma J and Pan Z. Junctional Membrane
Structure and Store-Operated Calcium Entry in Muscle
Cells. Front. Biosci. 2003, 8(1):
d242-d255 (review)
Ma J and Pan Z. Retrograde Activation of
Store-Operated Calcium Channel. Cell Calcium.
2003, 33: 375–384 (review)
Pan Z, Hirata Y, Nagaraj RY, Zhao J, Nishi M,
Hayek SM, Bhat MB, Takeshima H, Ma J. Co-expression
of mg29 and ryanodine receptor leads to apoptotic
cell death - effect mediated by intracellular Ca2+
release. J. Biol. Chem. 2004; 279:
19387 - 19390 (accelerated publication)
Hirata Y, Brotto M, Weisleder N, Chu Y, Lin P,
Zhao X, Thornton A, Komazaki S, Takeshima H, Ma J,
Pan Z. Uncoupling of store-operated Ca2+
entry through silencing of junctophilin genes.
Biophysical J. 2006; 90(12): 4418-27
|
