A. Significance
Intracellular trafficking is an essential cellular communication process in which membrane vesicles carrying lipids, proteins, and nucleic acids are taken up and transported through endosomes to lysosomes (termed endocytosis) and vesicles carrying macromolecules are delivered to the plasma membrane and outside of the cell (exocytosis) {Oka, 2005 #5437}. Uptake of external particles through endocytosis is required for prolific growth and differentiation. For example, uptake of transferrin provides iron necessary for growth and parasitism of the parasite Plasmodium falciparum {Rodriguez, 1986 #5445}. In contrast, the synaptic release of neurotransmitters, including dopamine and serotonin exemplifies…show more content…
By sharing only the N-terminal EH domains and CC region with ITSN1 plus a proline-rich (PR) region, Pan1 has a role in endocytosis and the organization of cortical actin through interactions with additional partner proteins, including EH proteins Ede1 and End3 {Wendland, 1998 #5492;Huang, 2007 #5510;Miliaras, 2004 #5491}. Pan1 homologs were identified from Candida species and Magnaporthe oryzae (Mo), but not Cn, indicating that Pan1-mediated endocytic trafficking is not universal among fungi ({Martin, 2007 #5481}, ZG Zhang and P Wang, unpublished data).
Cn is an encapsulated basidiomycetous fungus infecting both immunocompromised and healthy individuals causing life-threatening meningoencephalitis {Mitchell, 1995 #878}. It produces virulence factors including melanin, the polysaccharide capsule, and extracellular ureases and phospholipases {Kozel, 1995 #1696;Buchanan, 1998 #2608;engeler, 2000 #3148}. Previous studies showed that secretory transport is important in virulence {Rodrigues, 2009 #5368;Jesus, 2009 #5368} and that Cn contains proteins with a conserved function in exocytosis, such as Sav1, Sec6, and Sec14 {Yoneda, 2006 #5408;Panepinto, 2009 #5385;Chayakulkeeree, 2011 #5686}. We identified cryptococcal intersectin 1 (Cin1) as a novel endocytic adaptor protein that is important not only in intracellular transport but also in growth and virulence
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