Related Experiment Video
Updated: Nov 10, 2025
12:48
Induction of Endothelial Differentiation in Cardiac Progenitor Cells Under Low Serum Conditions
Published on: January 7, 2019
6.6K
Adhesion GPCR Latrophilin-2 Specifies Cardiac Lineage Commitment through CDK5, Src, and P38MAPK
Choon-Soo Lee1, Hyun-Jai Cho2, Jin-Woo Lee1
1Strategic Center of Cell & Bio Therapy, Seoul National University Hospital, Seoul 03080, Republic of Korea; Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Republic of Korea.
Stem Cell Reports
|April 2, 2021
Summary
Latrophilin-2 (LPHN2) is a novel cell-surface marker that effectively isolates cardiac progenitor cells and cardiomyocytes. This discovery advances understanding of cardiac differentiation and cell therapy development.
Area of Science:
- Cardiovascular Biology
- Stem Cell Biology
- Cell Signaling
Background:
- Identifying lineage-specific markers is crucial for developmental biology and cell therapies.
- Latrophilin-2 (LPHN2), an adhesion G-protein-coupled receptor, was investigated for its role in cardiac differentiation.
Purpose of the Study:
- To investigate the function of LPHN2 in cardiac differentiation.
- To identify molecular mechanisms underlying LPHN2-mediated cardiac differentiation.
- To establish LPHN2 as a marker for isolating cardiac progenitor cells (CPCs) and cardiomyocytes (CMCs).
Main Methods:
- Pluripotent stem cell (PSC) differentiation protocols were used.
- Cell sorting with an anti-LPHN2 antibody was performed.
- Lphn2 knockdown and knockout PSCs were generated.
- Phospho Explorer Antibody Array was employed to analyze signaling pathways.
Main Results:
- LPHN2 was selectively expressed in CPCs and CMCs during PSC differentiation.
- Anti-LPHN2 antibody-mediated cell sorting enriched CPCs and CMCs.
- Lphn2-deficient PSCs failed to express cardiac genes.
- LPHN2 signaling activated cyclin-dependent kinase 5 (CDK5), Src, and P38MAPK pathways.
Conclusions:
- LPHN2 serves as a valuable cell-surface marker for isolating CPCs and CMCs from PSCs.
- LPHN2 plays a critical role in cardiac differentiation through CDK5, Src, and P38MAPK signaling.
- These findings offer insights into cardiac differentiation mechanisms and potential cell therapy strategies.
Related Concept Videos
01:17Intracellular Signaling Affects Focal Adhesions
3.2K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
3.2K
01:09GPCRs Regulate Adenylyl Cylase Activity
6.3K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
6.3K
01:31Mechanism of Lamellipodia Formation
3.1K
Cells migrating in response to external stimuli form lamellipodia, which are thin membrane protrusions supported by a mesh of linked, branched, or unbranched actin filaments. These actin filaments interact with myosin motor proteins, creating the dynamic actomyosin complex within the cytoskeleton. Contractility, or the ability to generate contractile stress, is inherent to the actomyosin complex. It helps cells detect the stiffness of the surrounding ECM and exert contractile force for...
3.1K
01:11IP3/DAG Signaling Pathway
13.2K
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...
13.2K
01:25cAMP-dependent Protein Kinase Pathways
7.2K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
7.2K
01:07MAPK Signaling Cascades
6.9K
Mitogen-activated protein kinase, or MAPK pathway, activates three sequential kinases to regulate cellular responses such as proliferation, differentiation, survival, and apoptosis. The canonical MAPK pathway starts with a mitogen or growth factor binding to an RTK. The activated RTKs stimulate Ras, which recruits Raf or MAP3 Kinase (MAPKKK), the first kinase of the MAPK signaling cascade. Raf further phosphorylates and activates MEK or MAP2 Kinases (MAPKK), which in turn phosphorylates MAP...
6.9K