Characterization of the ESCRT pathway in Candida albicans.
2010-02
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Characterization of the ESCRT pathway in Candida albicans.
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2010-02
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Abstract
The human opportunistic pathogen Candida albicans has a signal transduction pathway
unique to fungi, called the Rim101 pathway. The Rim101 pathway regulates the
proteolytic activation of the transcription factor, Rim101, the activation of which is
required for growth at neutral-alkaline pH. Many genes regulated by Rim101 play a role
in C. albicans virulence, including genes involved in filamentation, cell wall structure,
adhesion, and nutrient acquisition. The Rim101 pathway consists of two complexes: a
signaling complex at the plasma membrane and a processing complex inside the cell, and
both of these complexes are required for Rim101 activation. Rim101 activation also
requires members of a second pathway, the endosomal sorting complex required for
transport (ESCRT) pathway. The ESCRT pathway is required to generate multivesicular
bodies prior to vesicle fusion with the vacuole. The ESCRT pathway consists of several
polyprotein complexes recruited sequentially to the endosomal membrane to generate an
intraluminal vesicle. The role of the ESCRT pathway has not been well characterized in
C. albicans, and study of the ESCRT pathway is complicated by the secondary effect
many ESCRT mutations have on Rim101 processing. These studies sought to separate iv
Abstract
The human opportunistic pathogen Candida albicans has a signal transduction pathway
unique to fungi, called the Rim101 pathway. The Rim101 pathway regulates the
proteolytic activation of the transcription factor, Rim101, the activation of which is
required for growth at neutral-alkaline pH. Many genes regulated by Rim101 play a role
in C. albicans virulence, including genes involved in filamentation, cell wall structure,
adhesion, and nutrient acquisition. The Rim101 pathway consists of two complexes: a
signaling complex at the plasma membrane and a processing complex inside the cell, and
both of these complexes are required for Rim101 activation. Rim101 activation also
requires members of a second pathway, the endosomal sorting complex required for
transport (ESCRT) pathway. The ESCRT pathway is required to generate multivesicular
bodies prior to vesicle fusion with the vacuole. The ESCRT pathway consists of several
polyprotein complexes recruited sequentially to the endosomal membrane to generate an
intraluminal vesicle. The role of the ESCRT pathway has not been well characterized in
C. albicans, and study of the ESCRT pathway is complicated by the secondary effect
many ESCRT mutations have on Rim101 processing. These studies sought to separate iv
Abstract
The human opportunistic pathogen Candida albicans has a signal transduction pathway
unique to fungi, called the Rim101 pathway. The Rim101 pathway regulates the
proteolytic activation of the transcription factor, Rim101, the activation of which is
required for growth at neutral-alkaline pH. Many genes regulated by Rim101 play a role
in C. albicans virulence, including genes involved in filamentation, cell wall structure,
adhesion, and nutrient acquisition. The Rim101 pathway consists of two complexes: a
signaling complex at the plasma membrane and a processing complex inside the cell, and
both of these complexes are required for Rim101 activation. Rim101 activation also
requires members of a second pathway, the endosomal sorting complex required for
transport (ESCRT) pathway. The ESCRT pathway is required to generate multivesicular
bodies prior to vesicle fusion with the vacuole. The ESCRT pathway consists of several
polyprotein complexes recruited sequentially to the endosomal membrane to generate an
intraluminal vesicle. The role of the ESCRT pathway has not been well characterized in
C. albicans, and study of the ESCRT pathway is complicated by the secondary effect
many ESCRT mutations have on Rim101 processing. These studies sought to separate ESCRT function from Rim101 function, and to investigate ESCRT pathway function in
C. albicans virulence. In these studies, ESCRT and Rim101 pathway separation is
demonstrated (1) at distinct domains on a single protein known to be part of both
pathways by using alanine scanning mutagenesis and (2) at ESCRT pathway complexes
by using deletion mutagenesis. The ESCRT pathway is demonstrated here to play a
wholly Rim101-independent role in C. albicans virulence.
Description
University of Minnesota Ph.D. dissertation. February 2010. Major: Microbiology, Immunology and Cancer Biology. Advisor: Dana Davis. 1 computer file (PDF);ix, 175 pages.
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Wolf, Julie Marie. (2010). Characterization of the ESCRT pathway in Candida albicans.. Retrieved from the University Digital Conservancy, https://hdl.handle.net/11299/59630.
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