Related Experiment Video

Updated: Mar 23, 2026

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy
08:27

Expression and Purification of the Human Lipid-sensitive Cation Channel TRPC3 for Structural Determination by Single-particle Cryo-electron Microscopy

Published on: January 7, 2019

10.1K

Defects in TRPM7 channel function deregulate thrombopoiesis through altered cellular Mg(2+) homeostasis and

Simon Stritt1,2, Paquita Nurden1,3, Remi Favier4,5

  • 1Chair of Experimental Biomedicine, University Hospital, University of Würzburg, Josef-Schneider-Strasse 2, 97078 Würzburg, Germany.

Nature Communications
|March 30, 2016
PubMed

Insights

Dysfunctional Transient Receptor Potential Melastatin-like 7 channel (TRPM7) impairs magnesium (Mg2+) regulation in megakaryocytes, causing macrothrombocytopenia. This platelet defect, linked to cytoskeletal issues, may affect human health.

Area of Science:

  • Hematology
  • Molecular Biology
  • Cardiovascular Research

Background:

  • Magnesium (Mg2+) is crucial for platelet function, yet its intracellular regulation in megakaryocytes (MKs) and platelets remains unclear.
  • Understanding these mechanisms is vital given Mg2+'s role in conditions like stroke and myocardial infarction.

Purpose of the Study:

  • To investigate the role of the Transient Receptor Potential Melastatin-like 7 channel (TRPM7) in regulating intracellular Mg2+ ([Mg2+]i) in MKs and platelets.
  • To determine the consequences of impaired TRPM7 function on platelet biogenesis and function.

Main Methods:

  • Utilized a mouse model with impaired TRPM7 channel function in MKs (Trpm7(fl/fl-Pf4Cre)).
  • Analyzed platelet biogenesis, cytoskeletal alterations, and proplatelet formation.
  • Investigated the effects of Mg2+ supplementation and non-muscle myosin IIA inhibition.

Main Results:

  • Impaired TRPM7 channel function in MKs led to macrothrombocytopenia in mice.
  • Cytoskeletal alterations and impaired proplatelet formation were observed in Trpm7(fl/fl-Pf4Cre) MKs.
  • Platelet biogenesis defects were rescued by Mg2+ supplementation or myosin IIA inhibition.

Conclusions:

  • TRPM7 channel dysfunction is a potential cause of macrothrombocytopenia in both mice and humans.
  • TRPM7 plays a critical role in maintaining platelet production through cytoskeletal regulation.
  • Further research into TRPM7 is warranted for understanding and potentially treating related bleeding disorders and cardiovascular conditions.

More Related Videos

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b10:20

Method for Identifying Small Molecule Inhibitors of the Protein-protein Interaction Between HCN1 and TRIP8b

Published on: November 11, 2016

9.1K
Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV412:09

Yeast Luminometric and Xenopus Oocyte Electrophysiological Examinations of the Molecular Mechanosensitivity of TRPV4

Published on: December 31, 2013

10.7K

Related Concept Videos

Receptor Tyrosine Kinases01:26

Receptor Tyrosine Kinases

Receptor tyrosine kinases or RTKs are membrane-bound receptors that phosphorylate specific tyrosine on protein substrates. RTKs regulate cellular growth, differentiation, survival, and migration. They contain an extracellular ligand binding domain, a transmembrane domain, and a cytosolic tail with intrinsic kinase activity. Several extracellular signaling molecules activate RTKs in one or more ways and relay the signal downstream. Ligands such as platelet-derived growth factor (PDGF) or...
20.5K
Enzyme-linked Receptors01:00

Enzyme-linked Receptors

Enzyme-linked receptors are proteins that act as both receptor and enzyme, activating multiple intracellular signals. This is a large group of receptors that include the receptor tyrosine kinase (RTK) family. Many growth factors and hormones bind to and activate the RTKs.
Neurotrophin (NT) receptors are a family of RTKs, including trkA, trkB, and trkC (tropomyosin-related kinase) receptors. TrkA is specific for nerve growth factor (NGF), neurotrophin-6, and neurotrophin-7. TrkB binds...
88.8K
Structure and Function of Platelets01:18

Structure and Function of Platelets

The cell fragments known as platelets are disc-shaped, with an average diameter of about 3 μm and a thickness of roughly 1 μm. They play a crucial role in the body's vascular clotting system, which also involves plasma proteins, blood cells, and blood vessel tissues.
Platelets are continually replenished, circulating in the bloodstream for 9-12 days before being removed by phagocytes, primarily in the spleen. A microliter of circulating blood contains between 150,000 and 450,000...
4.6K
Thermosensation01:43

Thermosensation

Peripheral thermosensation is the perception of external temperature. A change in temperature (on the surface of the skin and other tissues) is detected by a family of temperature-sensitive ion channels called Transient Receptor Potential, or TRP, receptors. These receptors are located on free nerve endings. Those detecting cold temperatures are closer to the surface of the skin than the nerve endings detecting warmth. These thermoTRP channels, while temperature selective, have relatively...
35.0K
IP3/DAG Signaling Pathway01:11

IP3/DAG Signaling Pathway

Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the  phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
15.8K
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
7.0K