mTOR kinase and the regulatory subunit of protein kinase A (PRKAR1A) spatially and functionally interact during autophagosorne maturation

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. RICE 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 alpha and LC3. We present experiments showing that mTOR colocalizes with RI alpha-, Rab7- and LC3-positive membranes in cultured cells. Because RI alpha 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.