Induction of TRPC6 Channel in Acquired Forms of Proteinuric Kidney Disease

Möller, Clemens; Wei, Changli; Altintas, Mehmet M.; Li, Jing; Greka, Anna; Ohse, Takamoto; Pippin, Jeffrey W.; Rastaldi, Maria Pia; Wawersik, Stefan; Schiavi, Susan C.; Henger, Anna; Kretzler, Matthias; Shankland, Stuart J.; Reiser, Jochen

doi:10.1681/asn.2006091010

Cited by 261 publications

(261 citation statements)

References 19 publications

Supporting

Mentioning

254

Contrasting

Unclassified

Order By: Relevance

“…Additional evidence suggests that TRPC6 plays an important role in podocyte function. TRPC6 is up-regulated in several acquired proteinuric kidney diseases (15), transgenic overexpression of wild-type or mutant TRPC6 in podocytes induces a mild glomerular phenotype (16), and TRPC6-deficient mice show some resistance to angiotensin II-induced proteinuria (17). TRPC6 has also been implicated in regulating blood pressure (18), pulmonary vascular tone and permeability (19 -24), cardiac hypertrophy (25)(26)(27), myofibroblast differentiation and associated wound healing (28,29), neuronal growth cone guidance (30), and platelet function (31).…”

Section: Gain-of-function Mutations In the Canonical Transient Receptmentioning

confidence: 99%

Gain-of-function Mutations in Transient Receptor Potential C6 (TRPC6) Activate Extracellular Signal-regulated Kinases 1/2 (ERK1/2)

Chiluiza

Krishna

Schumacher

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Signaling events affected by disease-associated mutations in TRPC6 are poorly defined. Results: Expression of mutant TRPC6 induces ERK1/2 activation via both cell-autonomous and non-cell-autonomous mechanisms. Conclusion: Mutant TRPC6 activates complex signaling pathways that lead to the release of paracrine factors activating ERK. Significance: Understanding the signaling pathways downstream of gain-of-function TRPC6 is crucial for understanding TRPC6-mediated biology and pathology.

show abstract

Section: Gain-of-function Mutations In the Canonical Transient Receptmentioning

confidence: 99%

Gain-of-function Mutations in Transient Receptor Potential C6 (TRPC6) Activate Extracellular Signal-regulated Kinases 1/2 (ERK1/2)

Chiluiza

Krishna

Schumacher

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…2,3 Furthermore, in several acquired human and experimental proteinuric kidney diseases, wild-type TRPC6 is induced in glomeruli at both the mRNA and protein levels. 4 These findings suggest high abundance of wild-type TRPC6 channels in podocytes contribute to a similar pathophysiology as the presence of mutated, overly active channels. Two major questions remain: What regulates TRPC6 channels in podocytes, and what effects does TRPC6-mediated Ca 2ϩ influx elicit in this cell?…”

mentioning

confidence: 89%

Sensitizing the Slit Diaphragm with TRPC6 Ion Channels

Möller¹,

Flesche²,

Reiser³

2009

Journal of the American Society of Nephrology

Self Cite

View full text Add to dashboard Cite

“…44 Moreover, disruption of the ultrafiltration process at the slit diaphragm might also be induced by Ca 2ϩ overload in podocytes, leading to apoptosis. Although experimental data stringently confirming these hypotheses are lacking, 45 AngII induces apoptosis in rat podocytes.…”

Section: Trpc6 and Podocyte Functionmentioning

confidence: 99%

Renal TRPathies

Dietrich¹,

Chubanov²,

Gudermann³

2010

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

One key function of the kidneys is the ultrafiltration of plasma by glomeruli to dispose of metabolic end products, excess electrolytes, and water. A vast array of ion channels and transporters are critical for filtration, secretion, and resorption of electrolytes to maintain homeostasis. In recent years, investigations have focused on several members of the large transient receptor potential (TRP) family of ion channels, because mutations in genes encoding members of three different TRP ion channel subfamilies have been linked to human kidney diseases. 1 Mutations in PKD1 (encoding TRPP1) and PKD2 (coding for TRPP2) occur at high frequency in individuals with autosomal dominant polycystic kidney disease. 2,3 The latter mutations and the pathophysiology of polycystic kidney disease are not discussed further in this overview because the topic has been covered by numerous insightful review articles. 4 -7 Missense and nonsense mutations in the gene coding for TRPC6 segregate with autosomal dominant FSGS, a kidney disease that leads to progressive renal failure. 8,9 Loss-of-function mutations in TRPM6 are also associated with hypomagnesemia with secondary hypocalcemia (HSH), a rare autosomal recessive disorder. 10 -12 The involvement of TRP channel mutations in hereditary kidney disease has shed new light on the molecular pathogenesis of renal failure and significantly enhanced our appreciation of the physiologic roles of TRP channels on tubular function. In this review, we focus exclusively on TRPC6 and TRPM6. TRPC6 AND PODOCYTE FUNCTIONTRPC6 is a nonselective cation channel and one of the seven members of the classical transient receptor potential (TRPC) family, which can be divided into subfamilies on the basis of amino acid similarity. Whereas TRPC1 and TRPC2 are almost unique, TRPC4 and TRPC5 share approximately 64% amino acid identity. TRPC3, TRPC6, and TRPC7 form a structural and functional subfamily displaying 65 to 78% identity at the amino acid level and share a common activator, diacylglycerol (DAG). 13 DAG is produced by phospholipase C isozymes activated after agonist binding to appropriate receptors, such as the interaction of angiotensin II (AngII) with AT 1 receptors.Like all TRPC family members, TRPC6 harbors an invariant sequence, the TRP box (containing the amino acid sequence EWKFAR), in its C-terminal tail as well as three ankyrin repeats in the N-terminus (Figure 1, A and B). The predicted transmembrane topology is similar to that of other TRP channels with intracellular N-and C-termini, six membrane-spanning helices (S1 through S6), and a presumed pore-forming loop (P) between S5 and S6 (Figure 1, A and B). As deduced from Northern blot analyses, TRPC6 channels are most prominently expressed in lung tissues, 14 where they ABSTRACTMany ion channels and transporters are involved in the filtration, secretion, and resorption of electrolytes by the kidney. In recent years, the superfamily of transient receptor potential (TRP) ion channels have received deserved attention because mutated TRP ch...

show abstract

Induction of TRPC6 Channel in Acquired Forms of Proteinuric Kidney Disease

Cited by 261 publications

References 19 publications

Gain-of-function Mutations in Transient Receptor Potential C6 (TRPC6) Activate Extracellular Signal-regulated Kinases 1/2 (ERK1/2)

Gain-of-function Mutations in Transient Receptor Potential C6 (TRPC6) Activate Extracellular Signal-regulated Kinases 1/2 (ERK1/2)

Sensitizing the Slit Diaphragm with TRPC6 Ion Channels

Renal TRPathies

Contact Info

Product

Resources

About