MTOR Kinase and the Regulatory Subunit of Protein Kinase A (PRKAR1A) Spatially and Functionally Interact during Autophagosome Maturation

Abstract

The regulatory subunit 1-alpha (RI-alpha) of protein kinase A (PKA) and the mTOR kinase are involved in a common pathway regulating mammalian autophagy. RI-alpha was found to localize on Rab7-positive late endosomes and on LC3-positive autophagosomal membranes in cultured cells. RI-alpha was also shown to physically interact with mTOR kinase and affect its phosphorylation and activity.1 In this addendum, we further explore the subcellular distribution of mTOR related to RI_ and LC3. We present experiments showing that mTOR colocalizes with RI-alpha-, Rab7- and LC3-positive membranes in cultured cells. Because RIa regulates the phosphorylation and activity of mTOR kinase, which we now show localizes on autophagosomal membranes, the possibility emerges that the RI-alpha-mTOR complex acts at the level of autophagosome maturation.Addendum to:Depletion of Type IA Regulatory Subunit (RI-alpha) of Protein Kinase A (PKA) in Mammalian Cells and Tissues Activates mTOR and Causes Autophagic DeficiencyM. Mavrakis, J. Lippincott-Schwartz, C.A. Stratakis and I. BossisHum Mol Genet 2006; 15:2962-71