Lymphoid signal transduction mechanisms linked to cellular prion protein

I E Mazzoni1, H C Ledebur, E Paramithiotis

  • 1Caprion Pharmaceuticals, Montreal, QC H4S 2C8, Canada.

Insights

The prion protein (PrPC) plays a role in immune function. Mice lacking PrPC show reduced splenocyte proliferation and altered protein signaling pathways, indicating its importance in immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Neuroscience

Background:

  • The cellular prion protein (PrPC) is a cell surface protein found in various cells, including lymphoid cells.
  • Its precise function, particularly in immune responses, remains incompletely understood.

Purpose of the Study:

  • To investigate the role of PrPC in immune cell activation and signaling.
  • To compare lectin-induced mitogenesis and cell signaling pathways in splenocytes from wild-type and PrPC-deficient mice.

Main Methods:

  • Splenocytes from wild-type and Prnp0/0 mice were stimulated with lectins (Concanavalin A and phytohemagglutinin).
  • Proliferation was assessed by 3H-thymidine incorporation.
  • Protein phosphorylation patterns (PKC, MAPK) and calcium fluxes were analyzed.

Main Results:

  • Prnp0/0 splenocytes exhibited significantly reduced proliferation, especially early in activation.
  • Defects in the phosphorylation of Protein Kinase C (PKC) alpha/beta and p44/42 MAPK were observed in Concanavalin A-activated Prnp0/0 splenocytes.
  • Calcium fluxes were comparable between wild-type and Prnp0/0 splenocytes, suggesting they are not directly involved in the observed signaling defects.

Conclusions:

  • The absence of PrPC impairs splenocyte activation and proliferation.
  • PrPC appears to modulate PKCalpha/beta phosphorylation, impacting its role in regulating splenocyte mitosis.
  • These findings support a role for PrPC in modulating immune function.

Related Concept Videos

Intracellular Signaling Cascades01:24

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...
Intracellular Signaling Cascades01:24

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...
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,...
Amplifying Signals via Second Messengers01:15

Amplifying Signals via Second Messengers

Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
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...
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 produces two-second...