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Review
. 2006 Aug;7(8):787-93.
doi: 10.1038/sj.embor.7400745.

The versatile nature of the calcium-permeable cation channel TRPP2

Affiliations
Review

The versatile nature of the calcium-permeable cation channel TRPP2

Aurélie Giamarchi et al. EMBO Rep. 2006 Aug.

Abstract

TRPP2 is a member of the transient receptor potential (TRP) superfamily of cation channels, which is mutated in autosomal dominant polycystic kidney disease (ADPKD). TRPP2 is thought to function with polycystin 1-a large integral protein-as part of a multiprotein complex involved in transducing Ca(2+)-dependent information. TRPP2 has been implicated in various biological functions including cell proliferation, sperm fertilization, mating behaviour, mechanosensation and asymmetric gene expression. Although its function as a Ca(2+)-permeable cation channel is well established, its precise role in the plasma membrane, the endoplasmic reticulum and the cilium is controversial. Recent studies suggest that TRPP2 function is highly dependent on the subcellular compartment of expression, and is regulated by many interactions with adaptor proteins. This review summarizes the most pertinent evidence about the properties of TRPP2 channels, focusing on the compartment-specific functions of mammalian TRPP2.

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Figures

Figure 1
Figure 1
Structural elements of the mammalian transient receptor potential cation channels and polycystin 1. ER, endoplasmic reticulum; GSK3, glycogen synthase kinase 3; PKD, polycystin; TRP, transient receptor potential family (TRPA, TRPC, TRPM, TRPML, TRPP, TRPV).
Figure 2
Figure 2
Regulatory carboxy-terminal domains of transient receptor potential polycystin proteins. (A) Sequence of human TRPP2 C-terminus. (B) Sequence alignment of the variable C-termini of human PKD2L1 (TRPP3), PKD2L2 (TRPP5) and PKD2 (TRPP2). Identical and similar residues are highlighted in black and grey, respectively. TRPP, transient receptor potential polycystin.
Figure 3
Figure 3
Compartment-specific functions of transient receptor potential polycystin 2. The various models for the localization-dependent functions of TRPP2 are shown. TRPP2 mediates Ca2+ influx at the plasma membrane (PM) and ciliary membrane (cilium), where it functions in a protein complex with polycystin 1 (PKD1) (1, 3) and possibly with other members of the TRP channel superfamily (TRPC1, TRPV4) (2). Ca2+ influx induced by shear flow in renal epithelial cells is triggered by bending of the luminal cilium and seemingly requires the presence of PKD1–TRPP2 complexes in the cilium (3). Mechanical stress results in activation of PKD1–TRPP2 complexes to allow Ca2+ influx either in the shaft or in the base of the cilium. TRPP2 acts as a Ca2+-release channel in the endoplasmic reticulum (ER), where it might interact with, and regulate, inositol-1,4,5-trisphosphate receptors (Ins(1,4,5)P3Rs) (4). Serine-phosphorylated TRPP2 sequesters Id2 in the cytoplasm and prevents it from entering the nucleus (5). PKD1 can undergo a proteolytic cleavage that releases its carboxy-terminal tail, which translocates to the nucleus and activates the transcription factor AP1 (6). Note that it is hypothesized that PKD1 targeted to the primary cilium is also cleaved at its GPCR proteolytic site (GPS). ERK, extracellular signal-regulated kinase; GPCR, G-protein coupled receptor; Id2, inhibitor of DNA binding 2; MEK, mitogen-activated protein kinase/ERK kinase; NFAT, nuclear factor of activated T-cells; PI3K, phosphatidyl-inositol 3-kinase; PKA, cAMP-dependent protein kinase; PKC, protein kinase C; REJ, receptor for egg jelly; TRPP2, transient receptor potential polycystin 2.
None
Aurélie Giamarchi
None
Françoise Padilla
None
Bertrand Coste
None
Matthieu Raoux
None
Marcel Crest
None
Eric Honoré
None
Patrick Delmas

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