Secretory Physiology Section, MPTB
NATIONAL INSTITUTES OF HEALTH/NIDCR
BUILDING 10 ROOM 1N113
10 CENTER DR MSC 1190
BETHESDA MD 20892-1190
Phone: (301) 496-5298
Fax: (301) 402-1228
E-mail: Dr. Indu S. Ambudkar
Research Interests
Ca2+ signaling mechanisms, TRP channels,Ca2+ channels and calcium transport proteins, role of Ca2+ in salivary gland growth and disease.
Education
B.Sc. Isabella Thoburn College, Lucknow, India. 1973
M.Sc. Lucknow University, Lucknow, India. 1975
Ph.D. Madurai Kamaraj University, Madurai, India. 1980
Mission
Studies in the Secretory Physiology Section (SPS) are primarily directed towards understanding the mechanisms by which a neurotransmitter signals a functional secretory response in salivary epithelial cells. Our previous studies have provided understanding of the molecular components involved in neurotransmitter-stimulated Ca2+ signaling in these cells. Recently, our efforts have been focused on the Ca2+ influx pathway in salivary gland cells, which has been suggested to be critical for the secretory function of the gland. Ca2+ influx in salivary gland cells occurs via the poorly understood "store-operated Ca2+ entry channel." Our studies are directed towards identification of (i) the molecular components, and (ii) the gating mechanism of the store-operated Ca2+ entry channel. Our studies utilize a variety of approaches, including electrophysiology, microfluorimetry, molecular biology, as well as biochemistry to determine whether the newly identified TRP family of ion channels proteins are involved in regulating/mediating store-operated Ca2+ influx. More recently, we have proposed that TRPC1 is a strong candidate for the Ca2+ influx channel mechanism in salivary gland acinar cells and potentially can be used as a target to modulate salivary gland function. Ongoing studies address the trafficking, assembly, and regulation of TRP channels and aim to establish the role of these channels in the function and development of salivary glands (a large image of the figure above is available).
Significant publications (since 2004)
Peer reviewed papers:
1. Fiorio Pla, A., Maric, D., Brazer,S-C, Giacobini, P, Liu, X., Chang Y.H., Ambudkar, I.S. and Barker, J.L. TRPC1 plays a role in bFGF/FGFR-1-induced Ca2+ entry and embryonic rat neural stem cell proliferation. J Neurosci. 25, 2687-2701 (2005).
2. Bandyopadhyay B., Liu, X., Swaim, W., Patterson, R. and Ambudkar, I.S. Apical localization of a functional TRPC3/TRPC6-Ca2+- signaling complex in polarized epithelial cells: role in apical Ca2+ influx. J. Biol. Chem., 280: 12908 – 12916 (2005).
3. Liu X, Bandyopadhyay BC, Singh BB, Groschner K, Ambudkar IS. Molecular Analysis of a Store-operated and 2-Acetyl-sn-glycerol-sensitive Non-selective Cation Channel: Heteromeric assembly of TRPC1-TRPC3. J Biol Chem. 280, 21600-21606. (2005).
4. Christos Chinopoulos, Anatoly A. Starkov, Sergey Grigoriev, Laurent M. Dejean, Kathleen W. Kinnally, Xibao Liu, Indu S. Ambudkar and Gary Fiskum. Diacylglycerols Activate Mitochondrial Cationic Channel(s) and Release Sequestered Ca2+. J. Bioenergetics and Biomembranes, 37, 237-247, (2005).
5. Xibao Liu, Bidhan Bandyopadhyay, Tetsuji Nakamoto, Brij Singh, Wolfgang Liedtke, James E. Melvin, and Indu Ambudkar. A Role for AQP5 in Activation of TRPV4 by Hypotonicity: concerted involvement of AQP5 AND TRPV4 in regulation of cell volume recovery. J. Biol. Chem., 281, 15485-15495, (2006).
6. H. Ong, X. Liu, A. Sharma, R. Hegde, and I. S. Ambudkar. Intracellular Ca2+ release via the ER translocon activates store-operated calcium entry. Pflugers Archives. Dec 14; [Epub ahead of print], (2006)
7. B. Pani, E. Cornatzer, W. Cornatzer, D.M. Shin, M.R Pittelkow, A. Hovnanian, I.S. Ambudkar, and B.B Singh. Upregulation of TRPC1 following SERCA2 gene silencing promotes cell survival: A potential role for TRPC1 in Darier’s Disease. Mol. Biol of Cell, 17, 4446-58 (2006).
8. H-L. Ong, K.T.Cheng, X. Liu, B. C. Bandyopadhyay, B.C. Paria, J. Soboloff, B. Pani, Y. Gwack, S. Srikanth, B.B. Singh, D. L. Gill, and I. S. Ambudkar. Dynamic assembly of TRPC1/STIM1/Orai1 ternary complex is involved in store operated calcium influx: Evidence for similarities in SOC and CRAC channel components. J Biol Chem Jan 15; [Epub ahead of print], (2007).
9. H-L. Ong, X. Liu, K. Tsaneva-Atanasova, B. B. Singh, B. C. Bandyopadhyay, W. D. Swaim, J. T. Russell, R. S. Hegde, A. Sherman, and I. S. Ambudkar. Relocalization of STIM1 for activation of store-operated Ca2+ entry is determined by the depletion of subplasma membrane endoplasmic reticulum Ca2+ store. Submitted.
10. X. Liu, K-T, Cheng, B. B. Singh, B. C. Bandyopadhyay, B. Pani, A. Dietrich, L. Birnbaumer, and I.S. Ambudkar. Attenuation of store-operated Ca2+ current impairs salivary gland fluid secretion in TRPC1(-/-) mice. Submitted
Reviews:
1. Ambudkar, I.S. Store-operated Membrane Channels: Calcium. Encyclopedia of Biological Chemistry, (2004).
2. Ambudkar, I.S. Cellular domains that contribute to Ca2+ entry events. Sci STKE. 243:PE32 (2004).
3. Ambudkar, I.S., Brazer, S.C., Liu, X., Lockwich, T., Singh, B. Plasma membrane localization of TRPC channels: role of caveolar lipid rafts. Novartis Found Symp. 258:63-70 (2004).
4. Ambudkar, I.S. Ca2+ signaling microdomains: platforms for assembly and regulation of TRPC channels. Trends in Pharmaceutical Sciences, (2006); 1:25-32. (Epub 2005 Dec 7).
5. Indu S. Ambudkar, Bidhan C. Bandyopadhyay Xibao Liu, Timothy P. Lockwich, Biman Paria, and Hwei L. Ong. Functional Organization of TRPC-Ca2+ Channels and Regulation of Calcium Microdomains. Cell Calcium. 40, 495-504. Epub 2006 Oct 9 (2006)
6. Indu S. Ambudkar. TRPC1: A core component of store operated calcium channel. Invited Review, Biochemical Society Transactions;35, 96-100. (2007).
7. Indu S. Ambudkar and Hwei L. Ong Organization and Function of TRPC channelosomes. Pflugers Arch,. In press, 2007.
8. Indu S. Ambudkar, Hwei Ling Ong, Xibao Liu, Bidhan Bandyopadhyay, and Kwong Tai Cheng. TRPC1: the link between functionally distinct store-operated calcium channels. Cell Calcium. In press, (2007).