The Arl3 and Arl1 GTPases co-operate with Cog8 to regulate selective autophagy via Atg9 trafficking

Area of Science:

• Cell Biology
• Molecular Biology
• Autophagy Research

Background:

• The Arl3-Arl1 GTPase cascade is vital for vesicle trafficking at the late Golgi and endosomes.
• The conserved oligomeric Golgi (COG) complex is essential for endosome-to-Golgi transport and the cytoplasm-to-vacuole targeting (Cvt) pathway.
• Selective autophagy pathways, like Cvt, are critical for cellular homeostasis.

Purpose of the Study:

• To investigate the role of the Arl3-Arl1 GTPase cascade in the Cvt pathway.
• To elucidate the interplay between the Arl3-Arl1 cascade, Cog8, and Atg9 trafficking in selective autophagy.
• To understand the regulation of Atg9 trafficking at the Golgi-endosome system.

Main Methods:

• Genetic analysis of Arl3-Arl1 and Cog8 mutants (arl3cog8Δ, arl1cog8Δ).
• Assessment of aminopeptidase I maturation in rich medium.
• Observation of Atg9 localization under normal and starvation conditions.
• Analysis of dynamic nucleotide binding in the Arl3-Arl1 cascade.

Main Results:

• The Arl3-Arl1 GTPase cascade cooperates with Cog8 to regulate the Cvt pathway through Atg9 trafficking.
• Mutants lacking Arl3-Arl1 and Cog8 show significant defects in aminopeptidase I maturation.
• Atg9 accumulates at the late Golgi in arl3cog8Δ and arl1cog8Δ cells under normal conditions, but not during starvation.
• The Arl3-Arl1 cascade influences the Cvt pathway via dynamic nucleotide binding.

Conclusions:

• The Arl3-Arl1 GTPase cascade and Cog8 are key regulators of Atg9 trafficking at the Golgi.
• Proper Atg9 trafficking, mediated by the Golgi-endosome system, is essential for efficient selective autophagy.
• Dynamic nucleotide binding by the Arl3-Arl1 cascade is involved in regulating the Cvt pathway.