Inhibition of the calcium store-operated calcium entry pathway by chemotactic peptide and by phorbol ester develops gradually and independently along differentiation of HL60 cells.

Abstract Orai1 was reported to function as a calcium channel subunit that facilitates store operated calcium entry (SOCE) in T cells and is necessary for formation of the immune synapse. We reasoned that SOCE via Orai1 might regulate PMNs activation during recruitment to inflamed endothelium. Orai1 function was assessed by real-time imaging of calcium transients as PMNs were stimulated to roll, arrest, and migrate on E-selectin and ICAM-1 in shear flow. Calcium entry was significantly reduced when Orai1 function was impaired by heterozygous knockout in a mouse model or by siRNA knockdown in HL-60 cells. Reduced Orai-1 expression correlated with the delayed onset of arrest and reduced ability to transition to a polarized migratory phenotype. Inhibition of SOCE by treatment with 2-APB, or blocking phospholipase C (PLC) mediated calcium store release with U73122, abrogated formyl peptide induced calcium elevation, and delayed subsequent cell arrest and polarization. These results suggest that calcium entry via Orai1 is the predominant SOCE that cooperates with cytoplasmic calcium store release in coordinating integrin-dependent PMN arrest and migration in the acute response to inflammation.

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Neuronal Store-Operated Calcium Entry Pathway as a Novel Therapeutic Target for Huntington's Disease Treatment

Chemistry & Biology ◽

10.1016/j.chembiol.2011.04.012 ◽

2011 ◽

Vol 18 (6) ◽

pp. 777-793 ◽

Cited By ~ 82

Author(s):

Jun Wu ◽

Hsin-Pei Shih ◽

Vladimir Vigont ◽

Lori Hrdlicka ◽

Len Diggins ◽

...

Keyword(s):

Huntington's Disease ◽

Huntington’S Disease ◽

Therapeutic Target ◽

Calcium Entry ◽

Disease Treatment ◽

Entry Pathway ◽

Store Operated Calcium Entry ◽

Novel Therapeutic

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A Microscopic View of the Store-Operated Calcium Entry-Pathway

ISRN Cell Biology ◽

10.1155/2013/237192 ◽

2013 ◽

Vol 2013 ◽

pp. 1-13 ◽

Cited By ~ 1

Author(s):

Jonathan Pacheco ◽

Luis Vaca

Keyword(s):

Plasma Membrane ◽

Protein Complexes ◽

Imaging Techniques ◽

Calcium Entry ◽

Point Of View ◽

Alternative Methods ◽

Entry Pathway ◽

Imaging Point ◽

Store Operated Calcium Entry ◽

Microscopy Techniques

Orai and STIM are the basic components of a highly complex and regulated mechanism for Ca2+ entry into the cell, known as store-operated calcium entry (SOCE). The activation of plasma membrane G-protein-coupled receptors associated with the phospholipase C cascade results in the rapid and massive production of inositol 1,4,5-triphosphate (IP3). This second messenger triggers the massive efflux of Ca2+ from the endoplasmic reticulum and into the cytosol, resulting in the oligomerization of the stromal interacting molecule (STIM1), a sensor of ER Ca2+. STIM1 oligomers (the so-called puncta) activate Orai channels at the plasma membrane, triggering the influx of Ca2+ into the cytosol. Several microscopy techniques have been implemented to study SOCE, resulting in stunning images of protein complexes assembling in real time. However, little attention has been paid to the findings about this complex mechanism from the imaging point of view, some of which appear to produce contradictory results. In the present review we gathered all the information about SOCE obtained with imaging techniques and contrast these findings with those obtained with alternative methods.

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