Murali Prakriya


PhD, Washington University in St. Louis

Driskill Graduate Program
Interdepartmental Neuroscience PhD Program

Lab Website

Office Phone: 312.503.7030
Lab Phone: 312.503.7031

E-mail

Research

Calcium (Ca2+) is a ubiquitous intracellular signaling messenger regulating a wide range of functions including enzyme activation, gene expression, chemotaxis, and neurotransmitter release. Cellular Ca2+ signals arise from the opening of Ca2+-permeable ion channels, a diverse family of membrane proteins. We study Ca2+ signals arising from store-operated Ca2+ channels (SOCs), a family of plasma membrane ion channels that are activated by a decrease in the calcium content of the endoplasmic reticulum (ER). Human patients with mutations in SOCs suffer from a devastating immunodeficiency, muscle weakness, and abnormalities in the skin, hair, and teeth, underscoring the vital importance of SOCs for human biology. We are studying the molecular and cellular mechanisms by which SOCs are activated and the mechanisms by which they regulate gene expression, immune cell function, and the development of neural stem cells. These studies are focused on a prototypic store-operated channel known as the Ca2+ release-activated Ca2+ (CRAC) channel. We have learnt that CRAC channels are activated by a unusual mechanism involving coordinated redistributions of the ER Ca2+ sensor and CRAC channel activator (a molecule called STIM1) and the CRAC channel, which results in both molecules gathering at the same peripheral sub-cellular sites. This type of activation process, where the stimulus brings the sensor and the channel together in opposite membranes is unusual among ion channels. We study the molecular and cellular events of this process by patch-clamp electrophysiology, biophysical and structural approaches, and various live-cell imaging techniques such as fluorescence resonance energy transfer (FRET) microscopy, total internal reflection (TIRF) microscopy, and calcium imaging. Research projects in my laboratory span from the single molecule level (to understand how store-operated Ca2+ channels operate), high-resolution subcellular levels (to understand the functional organization of Ca2+ signaling networks), to macroscopic whole-animal levels (to understand the physiological roles of Ca2+ signals for gene expression, proliferation, and neural development).

 

Selected Publications

Prakriya M and Lewis RS (2015).  Store-operated calcium channels. Physiological Reviews. 95(4):1383-436.

Tirado-Lee L, Yamashita M, and Prakriya M (2015) Conformational changes in the Orai1 C-terminus evoked by STIM1 binding. PloS One 10(6):e0128622.

Jairaman A, Yamashita M, Schleimer RP and Prakriya M (2015) Store-operated CRAC channels regulate PAR2-activated Ca2+ signals and cytokine production in airway epithelial cells. J Immunology 195(5):2122-33.

Yamashita M and Prakriya M (2014) Divergence of Ca2+ selectivity and equilibrium Ca2+ blockade in a Ca2+ release-activated Ca2+ channel. Journal of General Physiology 153: 325-343.

Somasundaram A, Shum AK, McBride HJ, Kessler JA, Feske S, Miller RJ, and Prakriya M (2014) Store-operated CRAC channels regulate gene expression and proliferation in neural progenitor cells. Journal of Neuroscience, 34: 9107-9123.

McNally BA, Somasundaram A, Jairaman A, and Prakriya, M (2013). The C- and N-terminal STIM1 binding sites on Orai1 are required for both trapping and gating of CRAC channels. Journal of Physiology, 591: 2833-2850.

McNally BA, Somasundaram A, Yamashita M, Prakriya M (2012). Gated regulation of CRAC channel ion selectivity by STIM1. Nature. 482: 241-245.

 


Recent Photos

November 25, 2015