Nat Cell Biol. 2002 May;4(5):329-36.
The TRPM7 channel is inactivated by PIP(2) hydrolysis.
Runnels, L. W., Yue, L., Clapham, D. E.,
["Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, MA 02115, USA."]
["Howard Hughes Medical Institute, Children's Hospital, Harvard Medical School, Enders 1309, 320 Longwood Avenue, Boston, MA 02115, USA."]
TRPM7 (ChaK1, TRP-PLIK, LTRPC7) is a ubiquitous, calcium-permeant ion channel that is unique in being both an ion channel and a serine/threonine kinase. The kinase domain of TRPM7 directly associates with the C2 domain of phospholipase C (PLC). Here, we show that in native cardiac cells and heterologous expression systems, G alpha q-linked receptors or tyrosine kinase receptors that activate PLC potently inhibit channel activity. Numerous experimental approaches demonstrated that phosphatidylinositol 4,5-bisphosphate (PIP(2)), the substrate of PLC, is a key regulator of TRPM7. We conclude that receptor-mediated activation of PLC results in the hydrolysis of localized PIP(2), leading to inactivation of the TRPM7 channel.
PMID: 11941371

![]() ![]() ![]() ![]() ![]() |
![]() |
Screening
![]() |
||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Experimental screening | Non-experimental screening | Reference | ||||||||
TRP channel construct | Interactor source | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Organ/tissue | Sample type | |||
TRPM7 |
![]() |
PLCƣ1 | Inference | Prediction | 11941371 | |||||
TRPM7 |
![]() |
PLCƢ2 | Inference | Prediction | 11941371 | |||||
TRPM7 |
![]() |
PLCƢ3 | Inference | Prediction | 11941371 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

![]() ![]() ![]() ![]() ![]() |
![]() |
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 |
![]() |
PLCƢ1 | Fusion protein-pull down assay | Rat | 1352-1862 | E. coli | Rat | Full-length | HEK293T lysates | 11941371 |
TRPM7 |
![]() |
PLCƢ1 | Yeast two-hybrid | Rat | 1532-1862 | Yeast | Rat | 643-1216 | Yeast | 11941371 |
TRPM7 |
![]() |
PLCƢ2 | Fusion protein-pull down assay | Rat | 1352-1862 | E. coli | Rat | Full-length | HEK293T lysates | 11941371 |
TRPM7 |
![]() |
PLCƢ3 | Fusion protein-pull down assay | Rat | 1352-1862 | E. coli | Rat | Full-length | HEK293T lysates | 11941371 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

![]() ![]() ![]() ![]() ![]() |
![]() |
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 |
![]() |
PLCƢ2 | Co-immunoprecipitation | HEK293T | Rat | Full-length | Rat | Full-length | 11941371 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

![]() ![]() ![]() ![]() ![]() |
![]() |
Characterization
![]() |
||||||||||
---|---|---|---|---|---|---|---|---|---|---|
Binding region mapping | Stoichiometry | Affinity (Kd) | Reference | |||||||
TRP channel | Interactor | |||||||||
TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
TRPM7 |
![]() |
PLCƢ1 | Yeast two-hybrid | Rat | 1532-1862 | Rat | 643-797 | 11941371 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)

![]() ![]() ![]() ![]() ![]() |
![]() |
Functional consequence
![]() |
||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|
TRP channel | Interactor | Method | Post-translational modification | Subcellular trafficking | Activity | Reference | ||||||
TRPM7 |
![]() |
PLCƢ1 | Patch clamp | Inhibition | 11941371 | |||||||
TRPM7 |
![]() |
PLCƢ2 | Patch clamp | Inhibition | 11941371 | |||||||
TRPM7 |
![]() |
PLCƢ3 | Patch clamp | Inhibition | 11941371 |
(
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
