mTOR controls lysosome tubulation and antigen presentation in macrophages and dendritic cells

• DOI: 10.1091/mbc.e15-05-0272
• Publication Date: 2015-11-19T03:44:02Z
• Authors: Amra Saric; Victoria E. B. Hi...; Jason G. Kay; Johnathan Canton; Costin N. Antonescu; Roberto J. Botelho
• Keywords: 0301 basic medicine; Antigen Presentation; 0303 health sciences; ADP-Ribosylation Factors; Macrophages; TOR Serine-Threonine Kinases; Articles; Dendritic Cells; Endosomes; Mice, Inbred C57BL; Oncogene Protein v-akt; Toll-Like Receptor 4; Mice; Phosphatidylinositol 3-Kinases; Protein Transport; 03 medical and health sciences; RAW 264.7 Cells; Animals; Female; Lysosomes; Signal Transduction

Macrophages and dendritic cells exposed to lipopolysaccharide (LPS) convert their lysosomes from small, punctate organelles into a network of tubules. Tubular have been implicated in phagosome maturation, retention fluid phase, antigen presentation. There is growing appreciation that act as sensors stress the metabolic state cell through kinase mTOR. Here we show LPS stimulates mTOR required for LPS-induced lysosome tubulation secretion major histocompatibility complex II macrophages cells. Specifically, canonical phosphatidylinositol 3-kinase–Akt–mTOR signaling pathway regulates independently IRAK1/4 TBK. Of note, find treatment augmented levels membrane-associated Arl8b, lysosomal GTPase promotes kinesin-dependent movement periphery, an mTOR-dependent manner. This suggests may interface with Arl8b-kinesin machinery. To further support this notion, antagonists can block outward treated acetate but no effect retrograde upon removal. Overall our work provides tantalizing evidence plays role controlling morphology trafficking by modulating microtubule-based motor activity leukocytes.