Multiprotein signaling complexes and regulation of cardiac phenotype

Thomas M Vondriska1, Peipei Ping

  • 1Department of Physiology, Division of Cardiology, Cardiovascular Research Laboratory, David Geffen School of Medicine at University of California, Suite 1609 MRL Building, Los Angeles, 675 C.E. Young Drive, Los Angeles, CA 90095-1760, USA.

Insights

Multiprotein complexes are key to cell signaling and phenotype changes. Functional proteomics offers advanced methods to analyze these complexes in cardiac cells, overcoming limitations of classical techniques.

Area of Science:

  • Biochemistry and Molecular Biology
  • Cellular Signaling
  • Proteomics

Background:

  • Multiprotein complexes are increasingly recognized as critical mediators of signal transduction across diverse cell types.
  • Alterations in these complexes directly influence cellular signaling pathways and cellular phenotype.
  • Classical experimental methods struggle to comprehensively characterize complex multiprotein interactions.

Purpose of the Study:

  • To examine the role of functional proteomics in elucidating protein complex-based signaling in cardiac cells.
  • To review and evaluate state-of-the-art proteomic techniques for analyzing multiprotein complexes.
  • To provide a protein complex-centric view of cardiac cell signaling.

Main Methods:

  • Review of current literature on functional proteomics and multiprotein complex analysis.
  • Discussion of advanced proteomic approaches, including mass spectrometry-based techniques.
  • Evaluation of the strengths and limitations of various proteomic methodologies for complex analysis.

Main Results:

  • Functional proteomics provides powerful tools to map multiprotein complexes involved in cardiac signaling.
  • Specific proteomic techniques offer enhanced capabilities for characterizing complex stoichiometry and dynamics.
  • The review highlights the potential of proteomics to reveal novel signaling mechanisms in cardiac cells.

Conclusions:

  • Proteomics is essential for a comprehensive understanding of cardiac cell signaling through multiprotein complexes.
  • Advanced proteomic strategies are crucial for overcoming the limitations of traditional methods.
  • This approach facilitates a deeper insight into how protein complexes regulate cardiac function and phenotype.

Related Concept Videos

Assembly of Signaling Complexes01:30

Assembly of Signaling Complexes

Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interactions Between Signaling Pathways01:19

Interactions Between Signaling Pathways

Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Diversity in Cell Signaling Responses01:22

Diversity in Cell Signaling Responses

The physiological function of a cell and cellular communication are outcomes of a range of extrinsic signals, intracellular signaling pathways, and cellular responses. No two cell types express the same repertoire of signaling components. Receptors are highly selective for their cognate ligands, but once activated, they can alter multiple cellular processes such as DNA transcription, protein synthesis, and metabolic activity. 
Graded and Abrupt Responses
Some signaling systems generate...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
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,...
Intracellular Signaling Cascades01:43

Intracellular Signaling Cascades

Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...