Family ties of gated pores: evolution of the sensor module

Kumánovics, Attila; Levin, G. M.; Blount, Paul

doi:10.1096/fj.02-0238hyp

Cited by 65 publications

(58 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The expected pore region of PC2, as that of other TRP channels, is expected in between TM5 and TM6, with the P-loop in the center, which contains the conductance pore of the channel. TM1-4 contain the expected "sensor" region of the channel (59). This remains to be proven (as with other parts of the channel protein).…”

Section: The Pc2 Proteinmentioning

confidence: 92%

Regulation of calcium signaling by polycystin-2

Cantiello¹

2004

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

Autosomal dominant PKD (ADPKD) is a common lethal genetic disorder characterized by progressive development of fluid-filled cysts in the kidney and other target organs. ADPKD is caused by mutations in the PKD1 and PKD2 genes, encoding the transmembrane proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Although the function and putative interacting ligands of PC1 are largely unknown, recent evidence indicates that PC2 behaves as a TRP-type Ca 2ϩ -permeable nonselective cation channel. The PC2 channel is implicated in the transient increase in cytosolic Ca 2ϩ in renal epithelial cells and may be linked to the activation of subsequent signaling pathways. Recent studies also indicate that PC1 functionally interacts with PC2 such that the PC1-PC2 channel complex is an obligatory novel signaling pathway implicated in the transduction of environmental signals into cellular events. The present review purposely avoids issues of regulation of PC2 expression and trafficking and focuses instead on the evidence for the TRP-type cation channel function of PC2. How its role as a cation channel may unmask mechanisms that trigger Ca 2ϩ transport and regulation is the focus of attention. PC2 channel function may be essential in renal cell function and kidney development. Nonrenal-targeted expression of PC2 and related proteins, including the cardiovascular system, also suggests previously unforeseeable roles in signal transduction.kidney; autosomal dominant polycystic kidney disease; polycystin-1; transient receptor potential channels; nonselective cation channels; calcium channels THIS REVIEW PURPOSELY AVOIDS detailing regulatory aspects of polycystin-2 (PC2) trafficking and developmental expression and cellular location of the channel protein, including cell biological issues of autosomal dominant polycystic kidney disease (ADPKD), for which highly comprehensive reviews can be found (49,84,137). This review focuses instead on the description of PC2 as a channel, its structural and functional similarities with other related transient receptor potential (TRP) channels, to which family it is a recent addition, and potential roles of PC2 in Ca 2ϩ signaling. Educated guesses can be drawn insofar as PC2 function, regulation, and/or interaction with other proteins are concerned, in particular new information on the molecular interaction with PC1 and expected regulation found in other TRP channels.

show abstract

Section: The Pc2 Proteinmentioning

confidence: 92%

Regulation of calcium signaling by polycystin-2

Cantiello¹

2004

American Journal of Physiology-Renal Physiology

View full text Add to dashboard Cite

show abstract

“…A group of MscL relatives form a separate family of MS channels, encompassing Gram-negative and Gram-positive bacteria (Fig. 4A), as well as representatives from Archaea and fungi (Kumánovics et al, 2003;Martinac and Kloda, 2003;Pivetti et al, 2003). The MscS relatives are more diverse, including several representatives from bacteria, Archaea, fungi and plants (Kloda and Martinac, 2002;Martinac and Kloda, 2003;Pivetti et al, 2003) (Fig.…”

Section: Prokaryotic Ms Channel Familiesmentioning

confidence: 99%

Mechanosensitive ion channels: molecules of mechanotransduction

Martinac

2004

Journal of Cell Science

494

352

View full text Add to dashboard Cite

Cells respond to a wide variety of mechanical stimuli, ranging from thermal molecular agitation to potentially destructive cell swelling caused by osmotic pressure gradients. The cell membrane presents a major target of the external mechanical forces that act upon a cell, and mechanosensitive (MS) ion channels play a crucial role in the physiology of mechanotransduction. These detect and transduce external mechanical forces into electrical and/or chemical intracellular signals. Recent work has increased our understanding of their gating mechanism, physiological functions and evolutionary origins. In particular, there has been major progress in research on microbial MS channels. Moreover, cloning and sequencing of MS channels from several species has provided insights into their evolution, their physiological functions in prokaryotes and eukaryotes, and their potential roles in the pathology of disease.

show abstract

“…The cytosolic enzyme domains of TPTE and TPIP have 35% and 37% sequence identity with PTEN and almost the same catalytic active site, suggesting that all may have similar substrate specificity. Unlike PTEN, TPTE and TPIP have N-terminal transmembrane domains that resemble the voltage sensor of VSP and of voltagegated ion channels (59). Recently, a chimera of the voltage sensor of TPTE with the pore domain of the bacterial voltage-gated potassium channel was shown to reconstitute functional voltagegated channel activity (7).…”

Section: Discussionmentioning

confidence: 99%

Phosphoinositide 5- and 3-phosphatase activities of a voltage-sensing phosphatase in living cells show identical voltage dependence

Keum

Kruse

Kim

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Voltage-sensing phosphatases (VSPs) are homologs of phosphatase and tensin homolog (PTEN), a phosphatidylinositol 3,4-bisphosphate [PI(3,4)P2] and phosphatidylinositol 3,4,5-trisphosphate [PI(3,4,5)P3] 3-phosphatase. However, VSPs have a wider range of substrates, cleaving 3-phosphate from PI(3,4)P2 and probably PI(3,4,5)P3 as well as 5-phosphate from phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and PI(3,4,5)P3 in response to membrane depolarization. Recent proposals say these reactions have differing voltage dependence. Using Förster resonance energy transfer probes specific for different PIs in living cells with zebrafish VSP, we quantitate both voltage-dependent 5- and 3-phosphatase subreactions against endogenous substrates. These activities become apparent with different voltage thresholds, voltage sensitivities, and catalytic rates. As an analytical tool, we refine a kinetic model that includes the endogenous pools of phosphoinositides, endogenous phosphatase and kinase reactions connecting them, and four exogenous voltage-dependent 5- and 3-phosphatase subreactions of VSP. We show that apparent voltage threshold differences for seeing effects of the 5- and 3-phosphatase activities in cells are not due to different intrinsic voltage dependence of these reactions. Rather, the reactions have a common voltage dependence, and apparent differences arise only because each VSP subreaction has a different absolute catalytic rate that begins to surpass the respective endogenous enzyme activities at different voltages. For zebrafish VSP, our modeling revealed that 3-phosphatase activity against PI(3,4,5)P3 is 55-fold slower than 5-phosphatase activity against PI(4,5)P2; thus, PI(4,5)P2 generated more slowly from dephosphorylating PI(3,4,5)P3 might never accumulate. When 5-phosphatase activity was counteracted by coexpression of a phosphatidylinositol 4-phosphate 5-kinase, there was accumulation of PI(4,5)P2 in parallel to PI(3,4,5)P3 dephosphorylation, emphasizing that VSPs can cleave the 3-phosphate of PI(3,4,5)P3.

show abstract

Family ties of gated pores: evolution of the sensor module

Cited by 65 publications

References 47 publications

Regulation of calcium signaling by polycystin-2

Regulation of calcium signaling by polycystin-2

Mechanosensitive ion channels: molecules of mechanotransduction

Phosphoinositide 5- and 3-phosphatase activities of a voltage-sensing phosphatase in living cells show identical voltage dependence

Contact Info

Product

Resources

About