A new cellular garbage control pathway with relevance for human neurodegenerative diseases

July 18, 2014
The newly identified proteins, termed CUET proteins (shown in red), recognize toxic protein aggregates and target the whole complex to the cellular waste disposal and recycling station, the lysosome. Credit: Stefan Jentsch, MPI of Biochemistry

Proteins, the components of our body that execute, control and organize basically all functions in our cells, are made out of strings of amino acids, which – like an origami - are folded into specific and complex three-dimensional structures according to their desired functions. However, since folding and maintaining of such structures is highly sensitive to cellular or environmental stress, proteins can potentially misfold or form clumps (aggregates). Such undesired protein waste can be toxic for cells and may even lead to cell death. Because several human neurodegenerative diseases are known to be linked to an accumulation of abnormal protein aggregates, basic science aimed to understand how cells remove cellular garbage is elementary for designing strategies for a potential prevention or cure of such disorders.

Scientists in the laboratory of Stefan Jentsch at the MPIB now successfully used baker's yeast for screening for new cellular waste disposal pathways. Kefeng Lu, a postdoctoral researcher from China, discovered a new class of helper proteins (termed CUET proteins) present both in yeast and humans that recognize cellular garbage earmarked for disposal by an attached label in the form of the ubiquitously existing known as "ubiquitin". Importantly, these newly identified helper proteins channel the cellular garbage by a "self-eating" pathway (autophagy) to the lysosome, a compartment of cells dedicated for destruction and recycling. The Max Planck scientists could also show that a toxic protein related to the abnormal, aggregate-forming protein "huntingtin" of patients with the neurodegenerative Huntington's disease is efficiently destroyed by the newly identified pathway. Remarkably, this pathway seems specific for aggregated proteins like huntingtin and appears to be more potent than previously discovered cellular garbage disposal mechanisms.

Because the identified cellular disposal mechanism operates in yeast as well, the researches will now take full advantage of its powerful experimental possibilities to investigate this pathway further. A detailed analysis of this mechanism will be crucial to understand how aggregate-forming proteins lead to human diseases and may help to develop concepts for possible disease preventions.

Explore further: Culprit implicated in neurodegenerative diseases also critical for normal cells

Related Stories

Recommended for you

Researchers grow retinal nerve cells in the lab

November 30, 2015

Johns Hopkins researchers have developed a method to efficiently turn human stem cells into retinal ganglion cells, the type of nerve cells located within the retina that transmit visual signals from the eye to the brain. ...

Shining light on microbial growth and death inside our guts

November 30, 2015

For the first time, scientists can accurately measure population growth rates of the microbes that live inside mammalian gastrointestinal tracts, according to a new method reported in Nature Communications by a team at the ...

Functional human liver cells grown in the lab

November 26, 2015

In new research appearing in the prestigious journal Nature Biotechnology, an international research team led by The Hebrew University of Jerusalem describes a new technique for growing human hepatocytes in the laboratory. ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.