Peptidyl-Prolyl Isomerase FKBP52 Controls Chemotropic Guidance of Neuronal Growth Cones via Regulation of TRPC1 Channel Opening

Shim, Sangwoo; Yuan, Joseph P.; Kim, Ju Young; Zeng, Weizhong; Huang, Guo N.; Milshteyn, Aleksandr; Kern, Dorothee; Muallem, Shmuel; Ming, Guo Li; Worley, Paul F.

doi:10.1016/j.neuron.2009.09.025

Cited by 68 publications

(73 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…All TRPCs are expressed in the brain and obviously have a significant role in regulation of the firing pattern of neurons (Ramsey et al 2006;Huang et al 2007;Boisseau et al 2008;Gokce et al 2009). They are involved in brain development, synaptogenesis, growth-cone guidance, dendritic growth, spine forming, and many other functions coupled to electrogenesis (Amaral and Pozzo-Miller 2007b;Wen et al 2007;Tai et al 2008; for a review, see Talavera et al 2008;Shim et al 2009). Persistent neuronal activity lasting seconds to minutes allows the transient storage of memory traces in entorhinal cortex and, thus, could play a major role in working memory.…”

Section: Trp Channels Depolarize Excitable Cells and Change Inwardly-mentioning

confidence: 99%

The Role of Transient Receptor Potential Cation Channels in Ca2+ Signaling

Gees

Colsoul²,

Nilius³

2010

Cold Spring Harbor Perspectives in Biology

382

361

View full text Add to dashboard Cite

The 28 mammalian members of the super-family of transient receptor potential (TRP) channels are cation channels, mostly permeable to both monovalent and divalent cations, and can be subdivided into six main subfamilies: the TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPP ( polycystin), TRPML (mucolipin), and the TRPA (ankyrin) groups. TRP channels are widely expressed in a large number of different tissues and cell types, and their biological roles appear to be equally diverse. In general, considered as polymodal cell sensors, they play a much more diverse role than anticipated. Functionally, TRP channels, when activated, cause cell depolarization, which may trigger a plethora of voltage-dependent ion channels. Upon stimulation, Ca 2þ permeable TRP channels generate changes in the intracellular Ca 2þ concentration, [Ca 2þ ] i , by Ca 2þ entry via the plasma membrane. However, more and more evidence is arising that TRP channels are also located in intracellular organelles and serve as intracellular Ca 2þ release channels. This review focuses on three major tasks of TRP channels: (1) the function of TRP channels as Ca 2þ entry channels; (2) the electrogenic actions of TRPs; and (3) TRPs as Ca 2þ release channels in intracellular organelles.T ransient receptor potential (TRP) channels constitute a large and functionally versatile family of cation-conducting channel proteins, which have been mainly considered as polymodal unique cell sensors. The first TRP channel gene was discovered in Drosophila melanogaster (Montell and Rubin 1989) in the analysis of a mutant fly whose photoreceptors failed to retain a sustained response to maintained light stimuli. So far, more than 50 TRP channels have been identified with representative members in many species. The evolutionary first TRP channels in protists, chlorophyte algae, choanoflagellates, yeast, and fungi are primary chemo-, thermo-, or mechanosensors (Cai 2008;Wheeler and Brownlee 2008;Chang et al. 2010;Matsuura et al. 2009). Many of these functions are remarkably conserved from protists, worms, and flies to humans (Montell 2005;Pedersen et al. 2005;Nilius et al. 2007;Damann et al. 2008). More than 50 trp genes have been cloned so far that comprise approximately 20% of the known genes encoding ion channels. In mammals, 28 TRP channels were found and classified according to homology into 6 subfamilies: TRPC (canonical), TRPV (vanilloid),

show abstract

Section: Trp Channels Depolarize Excitable Cells and Change Inwardly-mentioning

confidence: 99%

The Role of Transient Receptor Potential Cation Channels in Ca2+ Signaling

Gees

Colsoul²,

Nilius³

2010

Cold Spring Harbor Perspectives in Biology

382

361

View full text Add to dashboard Cite

show abstract

“…In hindsight, an early indication of the functional significance for FKBP51 and FKBP52 of the interface between the ␤ 4 -␤ 5 loop and the underlying ␤ 2 and ␤ 3a strands was the widespread use of a F67D,D68V double mutant as a presumed indicator for the participation of the peptidyl prolyl isomerase activity for these proteins in their biological functions, in particular for steroid receptor activity (15,(35)(36)(37)(38). More recently, in the context of their analysis of the effects of the L119P and P119L variants of FKBP51 and FKBP52 in the transcriptional activity of the steroid hormone receptor discussed above, Smith and colleagues (16) compared the F67D,D68V double mutant to other mutations that lay within the catalytic cleft to conclude that the steroid receptor activity does not depend upon prolyl isomerization catalysis.…”

Section: Structural Analysis Of the Interface Between The ␤ 4 -␤mentioning

confidence: 99%

Coupling of Conformational Transitions in the N-terminal Domain of the 51-kDa FK506-binding Protein (FKBP51) Near Its Site of Interaction with the Steroid Receptor Proteins

LeMaster

Mustafi

Brecher

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…This is an energy-demanding step in protein folding (17). Several other functions have also been assigned to the human FKBP family, such as regulation of Ca 2ϩ levels in muscles (18,19), regulation of immune activation (20), and chemotropic nerve guidance (21). In addition, it was also shown that immunophilin ligands, such as FK506, exhibit significant neuroregenerative and neuroprotective properties in cell culture and in animal models for neurodegeneration in general and in PD models in particular (22).…”

Section: Parkinson Disease (Pd)mentioning

confidence: 99%

Comparative Analysis of Different Peptidyl-Prolyl Isomerases Reveals FK506-binding Protein 12 as the Most Potent Enhancer of α-Synuclein Aggregation

Deleersnijder

Rompuy

Desender

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

FK506-binding proteins (FKBPs) are members of the immunophilins, enzymes that assist protein folding with their peptidyl-prolyl isomerase (PPIase) activity. Some non-immunosuppressive inhibitors of these enzymes have neuroregenerative and neuroprotective properties with an unknown mechanism of action. We have previously shown that FKBPs accelerate the aggregation of ␣-synuclein (␣-SYN) in vitro and in a neuronal cell culture model for synucleinopathy. In this study we investigated whether acceleration of ␣-SYN aggregation is specific for the FKBP or even the PPIase family. Therefore, we studied the effect of several physiologically relevant PPIases, namely FKBP12, FKBP38, FKBP52, FKBP65, Pin1, and cyclophilin A, on ␣-SYN aggregation in vitro and in neuronal cell culture. Among all PPIases tested in vitro, FKBP12 accelerated ␣-SYN aggregation the most. Furthermore, only FKBP12 accelerated ␣-SYN fibril formation at subnanomolar concentrations, pointing toward an enzymatic effect. Although stable overexpression of various FKBPs enhanced the aggregation of ␣-SYN and cell death in cell culture, they were less potent than FKBP12. When FKBP38, FKBP52, and FKBP65 were overexpressed in a stable FKBP12 knockdown cell line, they could not fully restore the number of ␣-SYN inclusion-positive cells. Both in vitro and cell culture data provide strong evidence that FKBP12 is the most important PPIase modulating ␣-SYN aggregation and validate the protein as an interesting drug target for Parkinson disease. Parkinson disease (PD)2 is the second most common neurodegenerative disorder. Accumulating evidence points to a causative role for the protein ␣-synuclein (␣-SYN) in PD (1-13), but the exact relationship between ␣-SYN aggregation and pathogenesis remains unresolved.We have recently shown that FKBP12, a member of the FK506-binding proteins (FKBPs), accelerates the aggregation of ␣-SYN in vitro (14). Furthermore, we demonstrated that FKBP12 and FKBP52 also enhance the aggregation of ␣-SYN in a neuronal cell culture model for synucleinopathy (15). FK506, a small molecule inhibitor of the FKBPs, counteracts this effect in a dose-dependent way. In addition, knockdown of FKBP12 and FKBP52 decreased the number of ␣-SYN aggregates in this cellular model and protected against cell death.FKBP12 and FKBP52 belong to the human FKBP family, of which currently 15 members have been identified. FKBPs are members of the immunophilins. These are enzymes that bind immunosuppressant drugs such as FK506 and have a peptidylprolyl cis-trans isomerase (PPIase) activity (16). They are able to accelerate the interconversion of cis-trans isomers of Xaa-Pro peptide bonds. This is an energy-demanding step in protein folding (17). Several other functions have also been assigned to the human FKBP family, such as regulation of Ca 2ϩ levels in muscles (18,19), regulation of immune activation (20), and chemotropic nerve guidance (21). In addition, it was also shown that immunophilin ligands, such as FK506, exhibit significant neuroregenerative and neuroprotec...

show abstract

Peptidyl-Prolyl Isomerase FKBP52 Controls Chemotropic Guidance of Neuronal Growth Cones via Regulation of TRPC1 Channel Opening

Cited by 68 publications

References 59 publications

The Role of Transient Receptor Potential Cation Channels in Ca2+ Signaling

The Role of Transient Receptor Potential Cation Channels in Ca2+ Signaling

Coupling of Conformational Transitions in the N-terminal Domain of the 51-kDa FK506-binding Protein (FKBP51) Near Its Site of Interaction with the Steroid Receptor Proteins

Comparative Analysis of Different Peptidyl-Prolyl Isomerases Reveals FK506-binding Protein 12 as the Most Potent Enhancer of α-Synuclein Aggregation

Contact Info

Product

Resources

About