To study autophagy to help understand the mechanisms of diseases associated with aging

Summary: Scientists have identified cellular and molecular mechanisms that regulate selective autophagy.

Sourcthe and: Warwick University

The study of autophagy – the process of intracellular processing and repair – has great potential in the fight against the aging process, bacterial and viral infections and diseases such as cancer, Alzheimer’s and Parkinson’s.

A team of researchers led by Ioannis Nezis, a professor at the University of Warwick’s School of Life Sciences, has identified molecular and cellular mechanisms that regulate selective autophagy in fruit flies. Drosophila melanogaster.

Although the function of these processes is increasingly being understood in mammals, this is one of the first studies in insects.

The study opens up new avenues for our understanding of the regulation of the Golgi complex by selective autophagy. The Golgi complex is a collection of flat sacs formed by the membranes inside the cell. It prepares proteins and fat molecules for transport and use inside and outside the cell.

Professor Nezis and his team used gene editing, confocal and electron microscopy to identify a new type of selective autophagy called Golgiphagia, in which cells degrade cell organelles called Golgi complexes by autophagy.

On paper, “GMAP is an Atg8a-activating protein that regulates Golgi circulation in Drosophila” published today in the journal Cell ReportsPhD students Ashrafur Rahman, Raksha Gohel, and colleagues describe how gene editing was used to create fruit flies that could not process certain proteins through autophagy.

The study opens up new avenues for our understanding of the regulation of the Golgi complex by selective autophagy. Image in public domain

Comparison of genetically modified flies with their wild counterparts: –

  • Atg8a’s LDS doc site is important in the implementation of selective autophagy
  • That selective autophagy regulates the size and morphology of the Golgi apparatus
  • The interaction of GMAP (Golgi microtubule-bound protein) Atg8a and the LIR motive in the 320-325 state is important for this interaction.
  • The LIR motive of GMAP is important Golgothagia

The study’s lead author, Ioannis Nezis, a professor at the University of Warwick’s School of Life Sciences, said:

“Understanding the molecular mechanisms of selective Golgi complex autophagy in cells will open up new avenues for research that could help explain the basic cellular mechanisms of disease.”

News about autophagy research

Author: Sheila Kiggins
A source: Warwick University
The connection: Sheila Kiggins – University of Warwick
Photo: Image in public domain

Original study: Open access.
“GMAP is an Atg8a-interacting protein that regulates Golgi circulation in Drosophila,” Ioannis Nezis et al. Cell Reports

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Abstract

GMAP is an Atg8a-interacting protein that regulates Golgi circulation in Drosophila.

Highlights

  • Atg8a-LDS mutants accumulate autophagy substrates and shorten their lifespan
  • Quantitative proteomic determination of GMAP in Atg8a-LDS mutants
  • GMAP interacts with Atg8a through the LIR motif
  • Atg8a-LDS and GMAP LIR motive mutants show Golgi’s long morphology

A result

Selective autophagy receptors and adapters include short-line motifs called LIR motives (LC3-interacting region) that are required to interact with Atg8-family proteins. LIR motifs bind to the hydrophobic pockets of the LIR motif (LDS) of the corresponding Atg8-family proteins. The physiological significance of LDS doc sites has not been clarified in vivo.

Here we show that Atg8a-LDS is a mutant Drosophila The flies accumulate autophagy substrates and shorten their lifespan.

Using quantitative proteomics to identify proteins accumulated in Atg8a-LDS mutants, we cis-Golgi protein GMAP (Golgi microtubule-associated protein) as a protein containing LIR motive that interacts with Atg8a. GMAP LIR mutant flies show a concentration of Golgi markers and a long Golgi morphology.

Our data mediate Goldli’s rotation through selective autophagy to regulate its morphology and size through the interaction of GMAP’s LIR motive with Atg8a.

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