Neuron. 2006 Nov 9;52(3):485-96.
The TRPM7 ion channel functions in cholinergic synaptic vesicles and affects transmitter release.
Krapivinsky, G., Mochida, S., Krapivinsky, L., Cibulsky, S. M., Clapham, D. E.,
["Howard Hughes Medical Institute, Cardiology, Children's Hospital Boston, 1309 Enders Building, 320 Longwood Avenue, Boston, MA, USA."]
["Howard Hughes Medical Institute, Cardiology, Children's Hospital Boston, 1309 Enders Building, 320 Longwood Avenue, Boston, MA, USA."]
A longstanding hypothesis is that ion channels are present in the membranes of synaptic vesicles and might affect neurotransmitter release. Here we demonstrate that TRPM7, a member of the transient receptor potential (TRP) ion channel family, resides in the membrane of synaptic vesicles of sympathetic neurons, forms molecular complexes with the synaptic vesicle proteins synapsin I and synaptotagmin I, and directly interacts with synaptic vesicular snapin. In sympathetic neurons, changes in TRPM7 levels and channel activity alter acetylcholine release, as measured by EPSP amplitudes and decay times in postsynaptic neurons. TRPM7 affects EPSP quantal size, an intrinsic property of synaptic vesicle release. Targeted peptide interference of TRPM7's interaction with snapin affects the amplitudes and kinetics of postsynaptic EPSPs. Thus, vesicular TRPM7 channel activity is critical to neurotransmitter release in sympathetic neurons.
PMID: 17088214
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
|
top
|
Screening
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Experimental screening | Non-experimental screening | Reference | ||||||||
| TRP channel construct | Interactor source | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
| TRPM7 |
|
SNAPIN | Yeast two-hybrid | Human | 87-326 | Human | Brain | cDNA library | 17088214 | |
| TRPM7 |
|
Synapsin1 | Inference | Prediction | 17088214 | |||||
| TRPM7 |
|
Synaptotagmin 1 | Inference | Prediction | 17088214 | |||||
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
|
top
|
Validation: In vitro validation
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Assay with recombinant proteins | Reference | |||||||||
| TRP channel construct | Interactor construct | |||||||||
| TRP channel | Interactor | Method | Species | Region | Expression system | Species | Region | Expression system | ||
| TRPM7 |
|
SNAPIN | Fusion protein-pull down assay | Human | 83-326 | In vitro translation | Human | Full-length | Not specified | 17088214 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
|
top
|
Validation: In vivo validation
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
| Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPM7 |
|
SNAPIN | Co-immunoprecipitation | Rat brain synaptic vesicle | 17088214 | |||||
| TRPM7 |
|
Synapsin1 | Co-immunoprecipitation | Rat brain synaptic vesicle | 17088214 | |||||
| TRPM7 |
|
Synapsin1 | Co-immunofluorescence staining | Rat SCG sympathetic neuron | 17088214 | |||||
| TRPM7 |
|
Synaptotagmin 1 | Co-immunoprecipitation | Rat brain synaptic vesicle | 17088214 | |||||
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
|
top
|
Characterization
|
||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
| TRP channel | Interactor | |||||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPM7 |
|
SNAPIN | Fusion protein-pull down assay | Human | 87-326 | Human | 43-68 | 17088214 | ||
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)



Screening