KEGG   PATHWAY: ocu04961
Entry
ocu04961                    Pathway                                
Name
Endocrine and other factor-regulated calcium reabsorption - Oryctolagus cuniculus (rabbit)
Description
Calcium (Ca2+) is essential for numerous physiological functions including intracellular signalling processes, neuronal excitability, muscle contraction and bone formation. Therefore, its homeostasis is finely maintained through the coordination of intestinal absorption, renal reabsorption, and bone resorption. In kidney, the late part of the distal convoluted tubule (DCT) and the connecting tubule (CNT) are the site of active Ca2+ transport and precisely regulate Ca2+ reabsorption. Following Ca2+ entry through TRPV5, Ca2+ bound to calbindin-D28K diffuses to the basolateral side, where it is extruded into the blood compartment through NCX1 and to a lesser extent PMCA1b. In the urinary compartment, both klotho and tissue kallikrein (TK) increase the apical abundance of TRPV5. In the blood compartment, PTH, 1,25(OH)2D3 and estrogen increase the transcription and protein expression of the luminal Ca2+ channels, calbindins, and the extrusion systems.
Class
Organismal Systems; Excretory system
Pathway map
ocu04961  Endocrine and other factor-regulated calcium reabsorption
ocu04961

Organism
Oryctolagus cuniculus (rabbit) [GN:ocu]
Gene
100351309  parathyroid hormone [KO:K05261]
100008785  PTH1R; parathyroid hormone/parathyroid hormone-related peptide receptor precursor [KO:K04585]
100008904  guanine nucleotide-binding protein G(s) subunit alpha isoforms XLas isoform X1 [KO:K04632]
100346323  neuroendocrine secretory protein 55 [KO:K04632]
100354934  adenylate cyclase type 6 isoform X8 [KO:K08046] [EC:4.6.1.1]
100340877  adenylate cyclase type 9 isoform X1 [KO:K08049] [EC:4.6.1.1]
100008815  PRKACA; cAMP-dependent protein kinase catalytic subunit alpha [KO:K04345] [EC:2.7.11.11]
100342212  cAMP-dependent protein kinase catalytic subunit beta isoform X3 [KO:K04345] [EC:2.7.11.11]
100008907  vitamin D3 receptor [KO:K08539]
100351261  estrogen receptor isoform X1 [KO:K08550]
100009364  TRPV5; transient receptor potential cation channel subfamily V member 5 [KO:K04974]
127491669  transient receptor potential cation channel subfamily V member 5 isoform X1 [KO:K04974]
100356074  klotho [KO:K14756] [EC:3.2.1.31]
100355909  dynamin-1 isoform X1 [KO:K01528] [EC:3.6.5.5]
108176538  dynamin-1 [KO:K01528] [EC:3.6.5.5]
100346468  dynamin-3 isoform X6 [KO:K01528] [EC:3.6.5.5]
100348451  dynamin-2 isoform X1 [KO:K23484] [EC:3.6.5.5]
103347267  AP-2 complex subunit alpha-2 [KO:K11824]
100347007  AP-2 complex subunit beta isoform X2 [KO:K11825]
100350578  AP-2 complex subunit mu [KO:K11826]
100349480  AP-2 complex subunit mu-like [KO:K11826]
103345727  AP-2 complex subunit sigma [KO:K11827]
100350456  clathrin light chain A isoform X2 [KO:K04644]
100351064  clathrin light chain B isoform X1 [KO:K04645]
100338178  clathrin heavy chain 1 isoform X1 [KO:K04646]
100351366  clathrin heavy chain 2 isoform X1 [KO:K04646]
100009072  RAB11A; ras-related protein Rab-11A [KO:K07904]
100008818  CALB1; calbindin [KO:K14757]
100349382  sodium/potassium-transporting ATPase subunit alpha-3 isoform X1 [KO:K01539] [EC:7.2.2.13]
100358269  sodium/potassium-transporting ATPase subunit alpha-4 isoform X1 [KO:K01539] [EC:7.2.2.13]
100008756  ATP1A2; sodium/potassium-transporting ATPase subunit alpha-2 [KO:K01539] [EC:7.2.2.13]
100302415  ATP1A1; sodium/potassium-transporting ATPase subunit alpha-1 [KO:K01539] [EC:7.2.2.13]
100009577  ATP1B2; sodium/potassium-transporting ATPase subunit beta-2 [KO:K01540]
100008749  ATP1B1; sodium/potassium-transporting ATPase subunit beta-1 [KO:K01540]
100008788  ATP1B3; sodium/potassium-transporting ATPase subunit beta-3 [KO:K01540]
100350113  protein ATP1B4 isoform X2 [KO:K01540]
103349229  sodium/potassium-transporting ATPase subunit gamma isoform X2 [KO:K01538]
127482585  sodium/potassium-transporting ATPase subunit gamma-like isoform X1 [KO:K01538]
100339605  sodium/calcium exchanger 3 isoform X1 [KO:K05849]
100328570  SLC8A1; sodium/calcium exchanger 1 precursor [KO:K05849]
100358483  sodium/calcium exchanger 2 [KO:K05849]
100356760  plasma membrane calcium-transporting ATPase 3 isoform X1 [KO:K05850] [EC:7.2.2.10]
100355180  plasma membrane calcium-transporting ATPase 2 isoform X1 [KO:K05850] [EC:7.2.2.10]
103351031  LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 4-like [KO:K05850] [EC:7.2.2.10]
100339414  LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 4-like [KO:K05850] [EC:7.2.2.10]
100356734  plasma membrane calcium-transporting ATPase 4 isoform X3 [KO:K05850] [EC:7.2.2.10]
100353865  plasma membrane calcium-transporting ATPase 4 isoform X1 [KO:K05850] [EC:7.2.2.10]
103351001  LOW QUALITY PROTEIN: plasma membrane calcium-transporting ATPase 4 [KO:K05850] [EC:7.2.2.10]
100009543  ATP2B1; plasma membrane calcium-transporting ATPase 1 [KO:K05850] [EC:7.2.2.10]
100101620  kallikrein 1 precursor [KO:K01325] [EC:3.4.21.35]
100338359  B2 bradykinin receptor isoform X1 [KO:K03916]
100340719  guanine nucleotide-binding protein G(q) subunit alpha [KO:K04634]
100348672  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-2 isoform X4 [KO:K05858] [EC:3.1.4.11]
100350395  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-4 isoform X1 [KO:K05858] [EC:3.1.4.11]
100341512  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-1 isoform X2 [KO:K05858] [EC:3.1.4.11]
103347536  1-phosphatidylinositol 4,5-bisphosphate phosphodiesterase beta-3 [KO:K05858] [EC:3.1.4.11]
100037720  PRKCA; protein kinase C alpha type [KO:K02677] [EC:2.7.11.13]
100037719  PRKCB; protein kinase C beta type isoform I [KO:K19662] [EC:2.7.11.13]
100009102  PRKCG; protein kinase C gamma type [KO:K19663] [EC:2.7.11.13]
Compound
C00076  Calcium cation
C00165  Diacylglycerol
C00238  Potassium cation
C00575  3',5'-Cyclic AMP
C00951  Estradiol-17beta
C01245  D-myo-Inositol 1,4,5-trisphosphate
C01330  Sodium cation
C01673  Calcitriol
Reference
  Authors
Boros S, Bindels RJ, Hoenderop JG
  Title
Active Ca(2+) reabsorption in the connecting tubule.
  Journal
Pflugers Arch 458:99-109 (2009)
DOI:10.1007/s00424-008-0602-6
Reference
  Authors
Lambers TT, Bindels RJ, Hoenderop JG
  Title
Coordinated control of renal Ca2+ handling.
  Journal
Kidney Int 69:650-4 (2006)
DOI:10.1038/sj.ki.5000169
Reference
  Authors
de Groot T, Bindels RJ, Hoenderop JG
  Title
TRPV5: an ingeniously controlled calcium channel.
  Journal
Kidney Int 74:1241-6 (2008)
DOI:10.1038/ki.2008.320
Reference
  Authors
Markadieu N, Bindels RJ, Hoenderop JG
  Title
The renal connecting tubule: Resolved and unresolved issues in Ca(2+) transport.
  Journal
Int J Biochem Cell Biol 43:1-4 (2011)
DOI:10.1016/j.biocel.2010.10.006
Reference
  Authors
Hoenderop JG, Nilius B, Bindels RJ
  Title
Calcium absorption across epithelia.
  Journal
Physiol Rev 85:373-422 (2005)
DOI:10.1152/physrev.00003.2004
Reference
  Authors
van Abel M, Hoenderop JG, Bindels RJ
  Title
The epithelial calcium channels TRPV5 and TRPV6: regulation and implications for disease.
  Journal
Naunyn Schmiedebergs Arch Pharmacol 371:295-306 (2005)
DOI:10.1007/s00210-005-1021-2
Reference
  Authors
Nijenhuis T, Hoenderop JG, Bindels RJ
  Title
TRPV5 and TRPV6 in Ca(2+) (re)absorption: regulating Ca(2+) entry at the gate.
  Journal
Pflugers Arch 451:181-92 (2005)
DOI:10.1007/s00424-005-1430-6
Reference
  Authors
Hoenderop JG, Nilius B, Bindels RJ
  Title
Epithelial calcium channels: from identification to function and regulation.
  Journal
Pflugers Arch 446:304-8 (2003)
DOI:10.1007/s00424-003-1045-8
Reference
  Authors
Gkika D, Topala CN, Chang Q, Picard N, Thebault S, Houillier P, Hoenderop JG, Bindels RJ
  Title
Tissue kallikrein stimulates Ca(2+) reabsorption via PKC-dependent plasma membrane accumulation of TRPV5.
  Journal
EMBO J 25:4707-16 (2006)
DOI:10.1038/sj.emboj.7601357
Reference
  Authors
Schoeber JP, Hoenderop JG, Bindels RJ
  Title
Concerted action of associated proteins in the regulation of TRPV5 and TRPV6.
  Journal
Biochem Soc Trans 35:115-9 (2007)
DOI:10.1042/BST0350115
Reference
  Authors
Renkema KY, Alexander RT, Bindels RJ, Hoenderop JG
  Title
Calcium and phosphate homeostasis: concerted interplay of new regulators.
  Journal
Ann Med 40:82-91 (2008)
DOI:10.1080/07853890701689645
Reference
  Authors
de Groot T, Lee K, Langeslag M, Xi Q, Jalink K, Bindels RJ, Hoenderop JG
  Title
Parathyroid hormone activates TRPV5 via PKA-dependent phosphorylation.
  Journal
J Am Soc Nephrol 20:1693-704 (2009)
DOI:10.1681/ASN.2008080873
Related
pathway
ocu04144  Endocytosis
ocu04530  Tight junction
KO pathway
ko04961   
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