Receptor-effector coupling by G proteins

A family of proteins called G proteins couples cell surface receptors to a variety of enzymes and ion channels. Since many cells contain several very similar G proteins, an important question is how signals remain specific as they cross the cell membrane.

Roles of G protein subunits in transmembrane signalling.

THE most characteristic change in progressive dementia of Alzheimer's type is a tissue deposit of amyloid β/A4 protein1, which is derived from its precursor protein APP (ref. 2). Structural alterations of APP are implicated in the pathogenesis of Alzheimer's disease, but it is not known how they cause the disease. Although APP has a receptor-like architecture2–5, is located on the neuronal surface6, and has a conserved cytoplasmic domain7, no receptor function has been demonstrated for APP. Here we report that APP forms a complex with Go, a major GTP-binding protein in brain. The cytoplasmic APP sequence His 657–Lys 676 shows a specific Go-activating function and is necessary for complex formation. Go protein treated with GTP-γS lost the ability to associate with APP. This suggests that APP is a receptor coupled to Go and that abnormal APP–Go signalling is involved in the Alzheimer's disease process.

Alzheimer amyloid protein precursor complexes with brain GTP-binding protein Go

Signal transduction by guanine nucleotide binding proteins

Antibodies directed against synthetic peptides distinguish between GTP-binding proteins in neutrophil and brain.

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2887%2981521-1

A new GTP-binding protein in brain tissues serving as the specific substrate of islet-activating protein, pertussis toxin

Guanine nucleotide-binding protein in sea urchin eggs serving as the specific substrate of islet-activating protein, pertussis toxin.

Immunohistochemical localization of guanine nucleotide-binding protein in rat retina.

Endocrine cells in pancreatic islets of Langerhans are immunoreactive to antibody against guanine nucleotide-binding protein (Go) purified from rat brain.

Masayuki Oinuma

Papers

A new GTP-binding protein in brain tissues serving as the specific substrate of islet-activating protein, pertussis toxin

Guanine nucleotide-binding protein in sea urchin eggs serving as the specific substrate of islet-activating protein, pertussis toxin.

Immunohistochemical localization of guanine nucleotide-binding protein in rat retina.

Endocrine cells in pancreatic islets of Langerhans are immunoreactive to antibody against guanine nucleotide-binding protein (Go) purified from rat brain.

Immunohistochemical analysis of the localization of guanine nucleotide-binding protein in the mouse brain