Clathrin- and Arp2/3-Independent Endocytosis in the Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>

ABSTRACT Clathrin-mediated endocytosis (CME) is conserved among eukaryotes and has been extensively analyzed at a molecular level. Here, we present an analysis of CME in the human fungal pathogen Candida albicans that shows the same modular structure as those in other fungi and mammalian cells. Intr...

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Autores principales:	Elias Epp, Elena Nazarova, Hannah Regan, Lois M. Douglas, James B. Konopka, Jackie Vogel, Malcolm Whiteway
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Lenguaje:	EN
Publicado:	American Society for Microbiology 2013
Materias:	Microbiology QR1-502
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spelling	oai:doaj.org-article:90acea0d518c4ab0af49a3309f632fd82021-11-15T15:42:47ZClathrin- and Arp2/3-Independent Endocytosis in the Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>10.1128/mBio.00476-132150-7511https://doaj.org/article/90acea0d518c4ab0af49a3309f632fd82013-11-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00476-13https://doaj.org/toc/2150-7511ABSTRACT Clathrin-mediated endocytosis (CME) is conserved among eukaryotes and has been extensively analyzed at a molecular level. Here, we present an analysis of CME in the human fungal pathogen Candida albicans that shows the same modular structure as those in other fungi and mammalian cells. Intriguingly, C. albicans is perfectly viable in the absence of Arp2/3, an essential component of CME in other systems. In C. albicans, Arp2/3 function remains essential for CME as all 15 proteins tested that participate in CME, including clathrin, lose their characteristic dynamics observed in wild-type (WT) cells. However, since arp2/3 cells are still able to endocytose lipids and fluid-phase markers, but not the Ste2 and Mup1 plasma membrane proteins, there must be an alternate clathrin-independent pathway we term Arp2/3-independent endocytosis (AIE). Characterization of AIE shows that endocytosis in arp2 mutants relies on actin cables and other Arp2/3-independent actin structures, as inhibition of actin functions prevented cargo uptake in arp2/3 mutants. Transmission electron microscopy (TEM) showed that arp2/3 mutants still formed invaginating tubules, cell structures whose proper functions are believed to heavily rely on Arp2/3. Finally, Prk1 and Sjl2, two proteins involved in patch disassembly during CME, were not correctly localized to sites of endocytosis in arp2 mutants, implying a role of Arp2/3 in CME patch disassembly. Overall, C. albicans contains an alternative endocytic pathway (AIE) that relies on actin cable function to permit clathrin-independent endocytosis (CIE) and provides a system to further explore alternate endocytic routes that likely exist in fungal species. IMPORTANCE There is a well-established process of endocytosis that is generally used by eukaryotic cells termed clathrin-mediated endocytosis (CME). Although the details are somewhat different between lower and higher eukaryotes, CME appears to be the dominant endocytic process in all eukaryotes. While fungi such as Saccharomyces cerevisiae have proven excellent models for dissecting the molecular details of endocytosis, loss of CME is so detrimental that it has been difficult to study alternate pathways functioning in its absence. Although the fungal pathogen Candida albicans has a CME pathway that functions similarly to that of S. cerevisiae, inactivation of this pathway does not compromise growth of yeast-form C. albicans. In these cells, lipids and fluid-phase molecules are still endocytosed in an actin-dependent manner, but membrane proteins are not. Thus, C. albicans provides a powerful model for the analysis of CME-independent endocytosis in lower eukaryotes.Elias EppElena NazarovaHannah ReganLois M. DouglasJames B. KonopkaJackie VogelMalcolm WhitewayAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 4, Iss 5 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Elias Epp Elena Nazarova Hannah Regan Lois M. Douglas James B. Konopka Jackie Vogel Malcolm Whiteway Clathrin- and Arp2/3-Independent Endocytosis in the Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
description	ABSTRACT Clathrin-mediated endocytosis (CME) is conserved among eukaryotes and has been extensively analyzed at a molecular level. Here, we present an analysis of CME in the human fungal pathogen Candida albicans that shows the same modular structure as those in other fungi and mammalian cells. Intriguingly, C. albicans is perfectly viable in the absence of Arp2/3, an essential component of CME in other systems. In C. albicans, Arp2/3 function remains essential for CME as all 15 proteins tested that participate in CME, including clathrin, lose their characteristic dynamics observed in wild-type (WT) cells. However, since arp2/3 cells are still able to endocytose lipids and fluid-phase markers, but not the Ste2 and Mup1 plasma membrane proteins, there must be an alternate clathrin-independent pathway we term Arp2/3-independent endocytosis (AIE). Characterization of AIE shows that endocytosis in arp2 mutants relies on actin cables and other Arp2/3-independent actin structures, as inhibition of actin functions prevented cargo uptake in arp2/3 mutants. Transmission electron microscopy (TEM) showed that arp2/3 mutants still formed invaginating tubules, cell structures whose proper functions are believed to heavily rely on Arp2/3. Finally, Prk1 and Sjl2, two proteins involved in patch disassembly during CME, were not correctly localized to sites of endocytosis in arp2 mutants, implying a role of Arp2/3 in CME patch disassembly. Overall, C. albicans contains an alternative endocytic pathway (AIE) that relies on actin cable function to permit clathrin-independent endocytosis (CIE) and provides a system to further explore alternate endocytic routes that likely exist in fungal species. IMPORTANCE There is a well-established process of endocytosis that is generally used by eukaryotic cells termed clathrin-mediated endocytosis (CME). Although the details are somewhat different between lower and higher eukaryotes, CME appears to be the dominant endocytic process in all eukaryotes. While fungi such as Saccharomyces cerevisiae have proven excellent models for dissecting the molecular details of endocytosis, loss of CME is so detrimental that it has been difficult to study alternate pathways functioning in its absence. Although the fungal pathogen Candida albicans has a CME pathway that functions similarly to that of S. cerevisiae, inactivation of this pathway does not compromise growth of yeast-form C. albicans. In these cells, lipids and fluid-phase molecules are still endocytosed in an actin-dependent manner, but membrane proteins are not. Thus, C. albicans provides a powerful model for the analysis of CME-independent endocytosis in lower eukaryotes.
format	article
author	Elias Epp Elena Nazarova Hannah Regan Lois M. Douglas James B. Konopka Jackie Vogel Malcolm Whiteway
author_facet	Elias Epp Elena Nazarova Hannah Regan Lois M. Douglas James B. Konopka Jackie Vogel Malcolm Whiteway
author_sort	Elias Epp
title	Clathrin- and Arp2/3-Independent Endocytosis in the Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
title_short	Clathrin- and Arp2/3-Independent Endocytosis in the Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
title_full	Clathrin- and Arp2/3-Independent Endocytosis in the Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
title_fullStr	Clathrin- and Arp2/3-Independent Endocytosis in the Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
title_full_unstemmed	Clathrin- and Arp2/3-Independent Endocytosis in the Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>
title_sort	clathrin- and arp2/3-independent endocytosis in the fungal pathogen <named-content content-type="genus-species">candida albicans</named-content>
publisher	American Society for Microbiology
publishDate	2013
url	https://doaj.org/article/90acea0d518c4ab0af49a3309f632fd8
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Clathrin- and Arp2/3-Independent Endocytosis in the Fungal Pathogen <named-content content-type="genus-species">Candida albicans</named-content>

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