Epidermal expression of the full-length extracellular calcium-sensing receptor is required for normal keratinocyte differentiation

2002 ◽  
Vol 192 (1) ◽  
pp. 45-54 ◽  
Author(s):  
Laszlo Komuves ◽  
Yuko Oda ◽  
Chia-ling Tu ◽  
Wen Han Chang ◽  
Chrystal L. Ho-Pao ◽  
...  
Keyword(s):  
Extracellular Calcium ◽  
Full Length ◽  
Keratinocyte Differentiation ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Epidermal Expression

Epidermal Keratinocyte Differentiation is Disrupted in Mice Lacking The Full Length Extracellular Calcium-Sensing Receptor

1997 ◽  
Vol 3 (S2) ◽  
pp. 185-186
Author(s):  
László G. Kömüves ◽  
Jonathan D. Harris ◽  
Chrystal Ho ◽  
Daniel D. Bikle
Keyword(s):  
In Situ Hybridization ◽  
Knockout Mice ◽  
Ion Homeostasis ◽  
Extracellular Calcium ◽  
Full Length ◽  
Keratinocyte Differentiation ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

The importance of the extracellular calcium-sensing receptor (CaR) in the stringent control of extracellular Ca2+ concentration is well established. However, the presence of CaR in tissues not directly involved in regulating mineral ion homeostasis suggests a role for CaR in local regulation of cellular functions. Although extracellular Ca2+ regulates the differentiation of keratinocytes, the role of CaR in the epidermis is not established. In this work using knockout mice lacking full length CaR, we sought to determine the role of CaR in epidermal differentiation.Dorsal skin of Casr−/− knockout mice lacking full length CaR, and Casr+/+ (wild type) control mice, aged 4 to 7 days after birth was fixed in 4% formaldehyde in PBS, and in 2.5% glutaraldehyde and 2% formaldehyde in 0.1 M cacodylate buffer. The samples were embedded in paraffin (for immunohistochemistry and for in situ hybridization) or in Spurr’s or LR White resins. Digoxigenin labeled antisense and sense RNA probes for loricrin and filaggrin were used for in situ hybridization.

An exon 5-less splice variant of the extracellular calcium-sensing receptor rescues absence of the full-length receptor in the developing mouse lung

2011 ◽  
Vol 37 (5) ◽  
pp. 269-278 ◽  
Author(s):  
Brenda Finney ◽  
William J. Wilkinson ◽  
Lydia Searchfield ◽  
Martin Cole ◽  
Stacey Bailey ◽  
...  
Keyword(s):  
Splice Variant ◽  
Extracellular Calcium ◽  
Full Length ◽  
Mouse Lung ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing

scholarly journals Structural basis for activation and allosteric modulation of full-length calcium-sensing receptor

2021 ◽  
Vol 7 (23) ◽  
pp. eabg1483
Author(s):  
Tianlei Wen ◽  
Ziyu Wang ◽  
Xiaozhe Chen ◽  
Yue Ren ◽  
Xuhang Lu ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Bound States ◽  
Hormone Secretion ◽  
Allosteric Modulation ◽  
Full Length ◽  
Structural Basis ◽  
Endocrine Disorders ◽  
Calcium Sensing Receptor ◽  
Calcium Sensing ◽  
Class C

Calcium-sensing receptor (CaSR) is a class C G protein–coupled receptor (GPCR) that plays an important role in calcium homeostasis and parathyroid hormone secretion. Here, we present multiple cryo–electron microscopy structures of full-length CaSR in distinct ligand-bound states. Ligands (Ca2+ and l-tryptophan) bind to the extracellular domain of CaSR and induce large-scale conformational changes, leading to the closure of two heptahelical transmembrane domains (7TMDs) for activation. The positive modulator (evocalcet) and the negative allosteric modulator (NPS-2143) occupy the similar binding pocket in 7TMD. The binding of NPS-2143 causes a considerable rearrangement of two 7TMDs, forming an inactivated TM6/TM6 interface. Moreover, a total of 305 disease-causing missense mutations of CaSR have been mapped to the structure in the active state, creating hotspot maps of five clinical endocrine disorders. Our results provide a structural framework for understanding the activation, allosteric modulation mechanism, and disease therapy for class C GPCRs.

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