Studying Autophagy to Help Us Understand the Mechanisms of Aging-Related Diseases


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

sourcee: University of Warwick

The study of autophagy – the recycling and repair process within cells – has huge potential to aid in fighting the aging process, bacterial and viral infections and diseases including cancer, Alzheimer’s and Parkinson’s.

A team of researchers led by Professor Ioannis Nezis from the School of Life Sciences at the University of Warwick, has identified the molecular and cellular mechanisms that regulate selective autophagy in the fruit fly Drosophila melanogaster.

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

The study opens new avenues in our understanding of the regulation of Golgi complex turnover by selective autophagy. The Golgi complex is a stack of flat sacs formed by membranes inside the cell. It prepares proteins and fat molecules for transportation and use in other places inside and outside the cell.

Professor Nezis and his team used gene editing, confocal and electron microscopy to identify a novel type of selective autophagy, termed Golgiphagy, meaning how cells degrade a cell organelle called Golgi complex by autophagy.

In the paper, ‘GMAP is an Atg8a-integrating protein that regulates Golgi turnover 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 unable to process specific proteins by autophagy.

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

Comparison of the gene-edited flies with their wild type counterparts showed:-

  • That Atg8a’s LDS docking site is important in the execution of selective autophagy
  • That selective autophagy regulates the size and morphology of the Golgi apparatus
  • That the GMAP (Golgi microtubule-associated protein) protein interacts with Atg8a and the LIR motif at position 320-325 is important for this interaction
  • That GMAP’s LIR motif is important Golgiphagy

Lead author of the research Professor Ioannis Nezis from the School of Life Sciences at the University of Warwick, said:

“Understanding the molecular mechanisms of selective autophagy of Golgi complex in cells will help open new avenues of research that will assist elucidating the underlying cellular mechanisms of diseases.”

About this autophagy research news

Author: Sheila Kiggins
Source: University of Warwick
Contact: Sheila Kiggins – University of Warwick
Image: The image is in the public domain

OriginalResearch: Open access.
“GMAP is an Atg8a-interacting protein that regulates Golgi turnover in Drosophila” by Ioannis Nezis et al. Cell Reports

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Abstract

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

highlights

  • Atg8a-LDS mutants accumulate autophagy substrates and have reduced lifespan
  • Quantitative proteomics identifies accumulation of GMAP in Atg8a-LDS mutants
  • GMAP interacts with Atg8a via a LIR motif
  • Atg8a-LDS and GMAP LIR motif mutants exhibit elongated Golgi morphology

Summary

Selective autophagy receptors and adapters contain short linear motifs called LIR motifs (LC3-interacting region), which are required for the interaction with the Atg8-family proteins. LIR motifs bind to the hydrophobic pockets of the LIR motif docking site (LDS) of the respective Atg8-family proteins. The physiological significance of LDS docking sites has not been clarified live.

Here, we show that Atg8a-LDS mutant Drosophila flies accumulate autophagy substrates and have reduced lifespan.

Using quantitative proteomics to identify the proteins that accumulate in Atg8a-LDS mutants, we identify the cis-Golgi protein GMAP (Golgi microtubule-associated protein) as a LIR motif-containing protein that interacts with Atg8a. GMAP LIR mutant flies exhibit accumulation of Golgi markers and elongated Golgi morphology.

Our data suggest that GMAP mediates the turnover of Golgi by selective autophagy to regulate its morphology and size via its LIR motif-mediated interaction with Atg8a.

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