TY - JOUR
T1 - Store-operated calcium entry
T2 - Pivotal roles in renal physiology and pathophysiology
AU - Chaudhari, Sarika
AU - Mallet, Robert T.
AU - Shotorbani, Parisa Y.
AU - Tao, Yu
AU - Ma, Rong
N1 - Funding Information:
The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: The work was supported by National Institutes of Health (NIH/NIDDK) [Grant number 5RO1DK079968-01] to R. Ma and a Postdoctoral Fellowship from American Heart Association Southwestern Affiliate [Grant number 20POST35210685] to S. Chaudhari.
Publisher Copyright:
© 2020 by the Society for Experimental Biology and Medicine.
PY - 2021/2
Y1 - 2021/2
N2 - Research conducted over the last two decades has dramatically advanced the understanding of store-operated calcium channels (SOCC) and their impact on renal function. Kidneys contain many types of cells, including those specialized for glomerular filtration (fenestrated capillary endothelium, podocytes), water and solute transport (tubular epithelium), and regulation of glomerular filtration and renal blood flow (vascular smooth muscle cells, mesangial cells). The highly integrated function of these myriad cells effects renal control of blood pressure, extracellular fluid volume and osmolality, electrolyte balance, and acid–base homeostasis. Many of these cells are regulated by Ca2+ signaling. Recent evidence demonstrates that SOCCs are major Ca2+ entry portals in several renal cell types. SOCC is activated by depletion of Ca2+ stores in the sarco/endoplasmic reticulum, which communicates with plasma membrane SOCC via the Ca2+ sensor Stromal Interaction Molecule 1 (STIM1). Orai1 is recognized as the main pore-forming subunit of SOCC in the plasma membrane. Orai proteins alone can form highly Ca2+ selective SOCC channels. Also, members of the Transient Receptor Potential Canonical (TRPC) channel family are proposed to form heteromeric complexes with Orai1 subunits, forming SOCC with low Ca2+ selectivity. Recently, Ca2+ entry through SOCC, known as store-operated Ca2+ entry (SOCE), was identified in glomerular mesangial cells, tubular epithelium, and renovascular smooth muscle cells. The physiological and pathological relevance and the characterization of SOCC complexes in those cells are still unclear. In this review, we summarize the current knowledge of SOCC and their roles in renal glomerular, tubular and vascular cells, including studies from our laboratory, emphasizing SOCE regulation of fibrotic protein deposition. Understanding the diverse roles of SOCE in different renal cell types is essential, as SOCC and its signaling pathways are emerging targets for treatment of SOCE-related diseases.
AB - Research conducted over the last two decades has dramatically advanced the understanding of store-operated calcium channels (SOCC) and their impact on renal function. Kidneys contain many types of cells, including those specialized for glomerular filtration (fenestrated capillary endothelium, podocytes), water and solute transport (tubular epithelium), and regulation of glomerular filtration and renal blood flow (vascular smooth muscle cells, mesangial cells). The highly integrated function of these myriad cells effects renal control of blood pressure, extracellular fluid volume and osmolality, electrolyte balance, and acid–base homeostasis. Many of these cells are regulated by Ca2+ signaling. Recent evidence demonstrates that SOCCs are major Ca2+ entry portals in several renal cell types. SOCC is activated by depletion of Ca2+ stores in the sarco/endoplasmic reticulum, which communicates with plasma membrane SOCC via the Ca2+ sensor Stromal Interaction Molecule 1 (STIM1). Orai1 is recognized as the main pore-forming subunit of SOCC in the plasma membrane. Orai proteins alone can form highly Ca2+ selective SOCC channels. Also, members of the Transient Receptor Potential Canonical (TRPC) channel family are proposed to form heteromeric complexes with Orai1 subunits, forming SOCC with low Ca2+ selectivity. Recently, Ca2+ entry through SOCC, known as store-operated Ca2+ entry (SOCE), was identified in glomerular mesangial cells, tubular epithelium, and renovascular smooth muscle cells. The physiological and pathological relevance and the characterization of SOCC complexes in those cells are still unclear. In this review, we summarize the current knowledge of SOCC and their roles in renal glomerular, tubular and vascular cells, including studies from our laboratory, emphasizing SOCE regulation of fibrotic protein deposition. Understanding the diverse roles of SOCE in different renal cell types is essential, as SOCC and its signaling pathways are emerging targets for treatment of SOCE-related diseases.
KW - Orai1
KW - STIM1
KW - Store-operated Ca channels
KW - TRPC
KW - extracellular matrix
KW - kidney disease
KW - mesangial cells
UR - http://www.scopus.com/inward/record.url?scp=85096934542&partnerID=8YFLogxK
U2 - 10.1177/1535370220975207
DO - 10.1177/1535370220975207
M3 - Review article
C2 - 33249888
AN - SCOPUS:85096934542
SN - 1535-3702
VL - 246
SP - 305
EP - 316
JO - Experimental Biology and Medicine
JF - Experimental Biology and Medicine
IS - 3
ER -