PXD026635

PXD026635 is an original dataset announced via ProteomeXchange.

Title	CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells
Description	Magnesium is essential for cellular life, but how it is homeostatically controlled still remains poorly understood. Here we report that members of CNNM family, which have been controversially implicated in both cellular Mg2+ influx and efflux, selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells. Co-expression of CNNMs with the channel markedly increased uptake of divalent cations, which is prevented by an inactivating mutation to the channel’s pore. Knockout of Trpm7 in cells or application of the TRPM7-channel inhibitor NS8593 also interfered with CNNM-stimulated divalent cation uptake. Conversely, knockout of CNNM3 and CNNM4 in HEK-293 cells significantly reduced TRPM7-mediated divalent cation entry, without affecting TRPM7 protein expression or its cell surface levels. Furthermore, we found that cellular overexpression of Phosphatases of Regenerating Liver (PRLs), a known CNNMs binding partner, stimulated TRPM7-dependent divalent cation entry and that CNNMs were required for this activity. Whole-cell electrophysiological recordings demonstrated that deletion of CNNM3 and CNNM4 from HEK-293 cells interfered with heterologously expressed and native TRPM7 channel function. We conclude that CNNMs employ the TRPM7 channel to mediate divalent cation influx and that CNNMs also possess separate TRPM7-independent Mg2+ efflux activities that contribute to CNNMs’ control of cellular Mg2+ homeostasis.
HostingRepository	PRIDE
AnnounceDate	2022-01-04
AnnouncementXML	Submission_2022-01-04_15:56:06.140.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Loren Runnels
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue
Instrument	Q Exactive HF; LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2021-06-10 22:44:46	ID requested
1	2021-11-15 05:18:37	announced
⏵ 2	2022-01-04 15:56:06	announced	2022-01-04: Updated project metadata.

Dataset with its publication pending

submitter keyword: TRPM7 CNNM3 CNNM4 CNMM2

Loren Runnels
contact affiliation	Rutgers RWJMS
contact email	runnellw@rwjms.rutgers
lab head
Loren Runnels
contact affiliation	Rutgers RWJMS
contact email	runnellw@rwjms.rutgers.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD026635
     1. Label: PRIDE project
     2. Name: CNNM proteins selectively bind to the TRPM7 channel to stimulate divalent cation entry into cells