Salk Institute: Immune receptors amplify “invader” signals by turning into mini-machines

Researchers at the Salk Institute in La Jolla, California, have discovered how immune receptors use a protein to amplify “invader” signals and attack a biological intruder. The T cell receptor that detects the intruder activates and releases copy after copy of a protein called ZAP70, becoming a mini-machine. This discovery sheds light on how T cells identify and react to pathogens — something researchers have for decades struggled to explain — and could help scientists develop better treatments for immune-based cancer and autoimmune diseases.

The research is supported in part by the NOMIS Foundation, and the finding was published on Nov. 21, 2016, in Nature Immunology. More details can be found in the Nov. 21 release by the Salk Institute.

The Salk Institute has been a NOMIS partner since 2008.

NOMIS researcher links heart disease, leukemia and aging disorders to dysfunction in nucleus

Salk Institute scientists in La Jolla, California have published in the Nov. 2 issue of Genes & Development a study demonstrating that the nuclear membrane acts not only as a driver of gene expression, but also disease. NOMIS board member and professor of molecular and cell biology at the Salk Institute Martin Hetzer is leading the team, who discovered that two proteins in the nuclear envelope, along with the membrane-spanning complexes they form, interact with parts of the genome to trigger key gene expression.

These proteins regulate the expression of super-enhancer-driven genes—i.e., those that help determine cell identity—and abnormal gene expression occurs when either of the proteins are suppressed. Experiments with human bone cancer and lung cancer cell lines confirmed that altering the proteins Nup153 or Nup93 result in faulty gene expression.

In the release published by Salk, Hetzer says, “People have thought the nuclear membrane is just a protective barrier, which is maybe the reason why it evolved in the first place. But there are many more regulatory levels that we don’t understand. And it’s such an important area because so far, every membrane protein that has been studied and found to be mutated or mis-localized, seems to cause a human disease.”

By better understanding this process, greater insight into diseases such as heart disease, leukemia and aging disorders, which are thought to be related to dysfunctional nuclear membrane components, can be gained.

The Salk Institute has been a NOMIS partner since 2008.