dictyNews
Electronic Edition
Volume 44, number 9
March 23, 2018
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Abstracts
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A short evolutionary journey across the HERC Ubiquitin Ligases
Enrico Bracco*, Cristina Panuzzo, Barbara Pergolizzi*
Journal of Immunological Sciences, in press
HECT ubiquitin ligases are key components of the eukaryotic ubiquitin
proteasome system controlling different cellular physiological aspects
as well as the genesis of several human diseases. Among the HECT
family, the HERC subfamily members are characterized by having one
or more RCC1-like domains, a C-terminal HECT domain and the
molecular mass ranging approximately from 120 kDa to 500 kDa. Due
to their large size , some of them are refractory to functional
characterization. We have recently identified and functionally
characterized a novel large HECT member in Dictyostelium discoideum
that, in many aspects, exhibits structural similarities with the mammalian
large HERC1. In the present mini-review, we shortly summarize and
revise the current phylogenetic history of HERC proteins among the
different living organisms.
submitted by: Enrico Bracco [[log in to unmask]]
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Cryptococcus neoformans escape from Dictyostelium amoeba by both
WASH-mediated constitutive exocytosis and vomocytosis.
Rhys A Watkins1 , Alexandre Andrews1 , Charlotte A Wynn1 , Caroline
Barisch2, Jason S King3* and Simon A Johnston1*
1 Department of Infections Immunity and Cardiovascular Disease,
Medical School, University of Sheffield, UK
2 University of Geneva, Switzerland
3 Department of Biomedical Sciences, University of Sheffield, UK
* Co-corresponding authors
Frontiers in Cellular and Infection Microbiology.
doi: 10.3389/fcimb.2018.00108
Cryptococcus neoformans is an environmental yeast that can cause
opportunistic infections in humans. As infecting animals does not form
part of its normal life-cycle, it has been proposed that the virulence traits
that allow cryptococci to resist immune cells were selected through
interactions with environmental phagocytes such as amoebae. Here, we
investigate the interactions between C. neoformans and the social
amoeba Dictyostelium discoideum. We show that like macrophages,
D. discoideum is unable to kill C. neoformans upon phagocytosis. Despite
this, we find that the yeast pass through the amoebae with an apparently
normal phagocytic transit and are released alive by constitutive exocytosis
after ~80 minutes. This is the canonical pathway in amoebae, used to
dispose of indigestible material after nutrient extraction. Surprisingly
however, we show that upon either genetic or pharmacological blockage
of constitutive exocytosis, C. neoformans still escape from D. discoideum
by a secondary mechanism. We demonstrate that constitutive exocytosis-
independent egress is stochastic and actin-independent. This strongly
resembles the non-lytic release of cryptococci by vomocytosis from
macrophages, which do not perform constitutive exocytosis and normally
retain phagocytosed material. Our data indicate that vomocytosis is
functionally redundant for escape from amoebae, which thus may not be
the primary driver for its evolutionary selection. Nonetheless, we show
that vomocytosis of C. neoformans is mechanistically conserved in hosts
ranging from amoebae to man, providing new avenues to understand this
poorly-understood but important virulence mechanism.
submitted by: Jason King [[log in to unmask]]
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