Published in Human Heredity
Objectives: Identifying drivers of complex traits from the noisy signals of genetic variation obtained from high-throughput genome sequencing technologies is a central challenge faced by human geneticists today. We hypothesize that the variants involved in complex diseases are likely to exhibit non-neutral evolutionary signatures. Uncovering the ev...
Published in Biochimica et biophysica acta. Molecular cell research
Acinar cell exocytosis requires spatiotemporal Ca2+ signals regulated through endoplasmic reticulum (ER) stores, Ca2+ATPases, and store-operated Ca2+ entry (SOCE). The secretory pathway Ca2+ATPase 2 (SPCA2) interacts with Orai1, which is involved in SOCE and store independent Ca2+ entry (SICE). However, in the pancreas, only a C-terminally truncate...
Published in Seminars in cell & developmental biology
Highly Ca2+ selective channels trigger a large variety of cellular signaling processes in both excitable and non-excitable cells. Among these channels, the Orai channel is unique in its activation mechanism and its structure. It mediates Ca2+ influx into the cytosol with an extremely small unitary conductance over longer time-scales, ranging from m...
Published in The Annals of otology, rhinology, and laryngology
Nuocytes are essential in innate type-2 immunity and contribute to the exacerbation of allergic rhinitis (AR). This study aimed to evaluate the intervention of Orai1 on the response of nuocytes from AR mice to interleukin (IL)-33. We established a murine model of AR. Nuocytes were obtained from the mouse nasal-associated lymphoid tissue. Then, we a...
Published in BMC Cancer
BackgroundThe endoplasmic reticulum (ER) Ca2+ sensor, stromal interaction molecule1 (STIM1) activates the plasma membrane (PM) channel Orai1 in order to mediate store-operated Ca2+ entry (SOCE) in response to ER store depletion. Enhanced expression of STIM1 in cancer tissue has been associated with poor patient prognosis. Therefore, this study inve...
Published in The Journal of physiology
Store-operated Ca2+ entry through Orai1 channels is a primary mechanism for Ca2+ entry in many cells and mediates numerous cellular effector functions ranging from gene transcription to exocytosis. Orai1 channels are amongst the most Ca2+ -selective channels known and are activated by direct physical interactions with the endoplasmic reticulum Ca2+...
Breast cancer is the most common type of cancer in women. It is a heterogeneous disease that ranges from the less undifferentiated luminal A to the more aggressive basal or triple negative breast cancer molecular subtype. Ca2+ influx from the extracellular medium, but more specifically store-operated Ca2+ entry (SOCE), has been reported to play an ...
Published in Kidney and Blood Pressure Research
Fibroblast growth factor 23 (FGF23) is released primarily from osteoblasts/osteocytes in bone. In cooperation with the transmembrane protein Klotho, FGF23 is a powerful inhibitor of 1α 25OH Vitamin D Hydroxylase (Cyp27b1) and thus of the formation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). As 1,25(OH)2D3 up-regulates intestinal calcium and phosphat...
Published in Cellular Physiology and Biochemistry
Background/Aims: STIM1 and Orai1 are the key components of store-operated Ca2+ entry (SOCE). Among the proteins involved in the regulation of SOCE, SARAF prevents spontaneous activation of SOCE and modulates STIM1 function. Methods: Cytosolic Ca2+ mobilization was estimated in fura-2-loaded cells using an epifluorescence inverted microscope. STIM1 ...
Published in Cellular Physiology and Biochemistry
Background/Aims: The neurodegenerative disease Chorea-Acanthocytosis (ChAc) is caused by loss-of-function-mutations of the chorein-encoding gene VPS13A. In ChAc neurons transcript levels and protein abundance of Ca2+ release activated channel moiety (CRAC) Orai1 as well as its regulator STIM1/2 are decreased, resulting in blunted store operated Ca2...
