TORC1 signaling in the budding yeast endomembrane system and control of cell-cell adhesion in pathogenic fungi

The rapamycin-sensitive TORC1 protein kinase is the central component of a conserved signal transduction cascade controlling cell growth in response to nutrients and growth factors. Groundbreaking studies are uncovering novel roles for the endomembrane vesicular trafficking system as a platform for TORC1 signaling. TORC1 components, regulators, and major effectors have been localized to late endosomes and the vacuolar periphery in yeast. Mutations in the class C Vps, Ego/Gse, and PAS protein complexes, involved in vesicular trafficking and protein sorting, in combination with mutation of the nonessential Tor1 kinase severely compromise or abolish cell growth. Class C Vps complex function sustains amino acid homeostasis for efficient TORC1 signaling. The Ego/Gse complex (EGOC) GTPase activity responds to amino acids to regulate permease sorting and activate TORC1 signaling. The emerging view is that amino acids are sensed in intimate association with the endomembrane system, which facilitates molecular interactions to enable TORC1 activation and signaling. Novel roles for TORC1 are also surfacing throughout the fungal kingdom. TORC1 regulates filamentous growth in fungi. In the human pathogen Candida albicans, TORC1 controls transcriptional programs including those involved in ribosome biogenesis and nutritional control. Remarkably, in C. albicans TORC1 governs expression of adhesins, which promote tissue adherence, biofilm formation, and virulence. These studies reveal TORC1 pathway wiring plasticity as pathogenic yeasts adapted to their host niche environments. A preeminent role for TORC1 signaling in fungal virulence has attracted interest in the use of rapamycin and its analogs in antifungal therapy. © 2010 Elsevier Inc.

Duke Scholars

Author Maria Elena Cardenas-Corona Molecular Genetics and Microbiology

Author Robert J Bastidas Integrative Immunobiology