| Title: | Secreted Acb1 Contributes to the Yeast-to-Hypha Transition in Cryptococcus neoformans |
| Author(s): | Xu X; Zhao Y; Kirkman E; Lin X; |
| Address: | "Department of Biology, Texas A&M University. College Station, Texas, USA. Department of Biology, Texas A&M University. College Station, Texas, USA xlin@bio.tamu.edu" |
| ISSN/ISBN: | 1098-5336 (Electronic) 0099-2240 (Print) 0099-2240 (Linking) |
| Abstract: | "Adaptation to stress by eukaryotic pathogens is often accompanied by a transition in cellular morphology. The human fungal pathogen Cryptococcus neoformans is known to switch between the yeast and the filamentous form in response to amoebic predation or during mating. As in the classic dimorphic fungal pathogens, the morphotype is associated with the ability of cryptococci to infect various hosts. Many cryptococcal factors and environmental stimuli, including pheromones (small peptides) and nutrient limitation, are known to induce the yeast-to-hypha transition. We recently discovered that secreted matricellular proteins could also act as intercellular signals to promote the yeast-to-hypha transition. Here we show that the secreted acyl coenzyme A (acyl-CoA)-binding protein Acb1 plays an important role in enhancing this morphotype transition. Acb1 does not possess a signal peptide. Its extracellular secretion and, consequently, its function in filamentation are dependent on an unconventional GRASP (Golgi reassembly stacking protein)-dependent secretion pathway. Surprisingly, intracellular recruitment of Acb1 to the secretory vesicles is independent of Grasp. In addition to Acb1, Grasp possibly controls the secretion of other cargos, because the graspDelta mutant, but not the acb1Delta mutant, is defective in capsule production and macrophage phagocytosis. Nonetheless, Acb1 is likely the major or the sole effector of Grasp in terms of filamentation. Furthermore, we found that the key residue of Acb1 for acyl binding, Y80, is critical for the proper subcellular localization and secretion of Acb1 and for cryptococcal morphogenesis" |
| Keywords: | Acyl Coenzyme A/metabolism Carrier Proteins/genetics/*metabolism Cryptococcus neoformans/*cytology/drug effects/growth & development/*metabolism DNA Mutational Analysis Hyphae/*cytology/drug effects/*growth & development Protein Binding; |
| Notes: | "MedlineXu, Xinping Zhao, Youbao Kirkman, Elyssa Lin, Xiaorong eng R01 AI097599/AI/NIAID NIH HHS/ R21 AI107138/AI/NIAID NIH HHS/ R01AI097599/AI/NIAID NIH HHS/ R21AI107138/AI/NIAID NIH HHS/ Research Support, N.I.H., Extramural 2015/12/08 Appl Environ Microbiol. 2015 Dec 4; 82(4):1069-1079. doi: 10.1128/AEM.03691-15. Print 2016 Feb 15" |
