dictyNews
Electronic Edition
Volume 48, number 21
October 14, 2022
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Abstracts
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Ras Inhibitors Gate Chemoattractant Concentration Range for
Chemotaxis through Controlling GPCR-mediated Adaptation and
Cell Sensitivity
Xuehua Xu* and Tian Jin
*Correspondence to [log in to unmask]
Frontiers in Immunology, in press
DOI: 10.3389/fimmu.2022.1020117
Chemotaxis plays an essential role in recruitment of leukocytes to
sites of inflammation. Eukaryotic cells sense chemoattractant with
G protein-coupled receptors (GPCRs) and chemotax toward
gradients with an enormous concentration range through adaptation.
Cells in adaptation no longer respond to the present stimulus but
remain sensitive to stronger stimuli. Thus, adaptation provides a
fundamental strategy for eukaryotic cells to chemotax through
a gradient. Ras activation is the first step in the chemosensing
GPCR signaling pathways that displays a transient activation
behavior in both model organism Dictyostelium discoideum and
mammalian neutrophils. Recently, it has been revealed that
C2GAP1 and CAPRI control the GPCR-mediated adaptation
in D. discoideum and human neutrophils, respectively. More
importantly, both Ras inhibitors regulate the sensitivity of the cells.
These findings suggest an evolutionarily conserved molecular
mechanism by which eukaryotic cells gate concentration range
of chemoattractants for chemotaxis.
Submitted by Xuehua Xu [[log in to unmask]]
_________________________________________________________
Dynamics of Actin Cytoskeleton and Their Signaling Pathways
during Cellular Wound Repair
S. Yumura 1, Md. Shahabe Uddin Talukder, Mst. Shaela Pervin,
Md. Istiaq Obaidi Tanvir, Takashi Matsumura, Koushiro Fujimoto,
Masahito Tanaka and Go Itoh
Published in Cells
https://www.mdpi.com/2073-4409/11/19/3166
The repair of wounded cell membranes is essential for cell survival.
Upon wounding, actin transiently accumulates at the wound site.
The loss of actin accumulation leads to cell death. The mechanism
by which actin accumulates at the wound site, the types of actin-
related proteins participating in the actin remodeling, and their
signaling pathways are unclear. We firstly examined how actin
accumulates at a wound site in Dictyostelium cells. Actin assembled
de novo at the wound site, independent of cortical flow. Next, we
searched for actin- and signal-related proteins targeting the wound
site. Fourteen of the examined proteins transiently accumulated at
different times. Thirdly, we performed functional analyses using
gene knockout mutants or specific inhibitors. Rac, WASP, formin,
the Arp2/3 complex, profilin, and coronin contribute to the actin
dynamics. Finally, we found that multiple signaling pathways related
to TORC2, the Elmo/Doc complex, PIP2-derived products, PLA2,
and calmodulin are involved in the actin dynamics for wound repair.
Submitted by Shigehiko Yumura [[log in to unmask]]
_________________________________________________________
Spindly is a nucleocytosolic O-fucosyltransferase in Dictyostelium
and related proteins are widespread in protists and bacteria
Hanke van der Wel1, Ana Maria Garcia4,ϑ, Elisabet
Gas-Pascual1, Macy M. Willis1, Hyun W. Kim1, Giulia Bandini2,#,
Maissa Mareme Gaye3,§, Catherine E. Costello3,
John Samuelson2 and Christopher M. West5,*
1Department of Biochemistry and Molecular Biology, University
of Georgia, Athens, GA 30602
2Department of Molecular and Cell Biology, Boston University
Henry Goldman School of Dental Medicine, Boston, MA 02118
3Center for Biomedical Mass Spectrometry, Department of
Biochemistry, Boston University School of Medicine, Boston,
MA, 02118
4Department of Biochemistry and Molecular Biology, University
of Oklahoma Health Sciences Center, Oklahoma City, OK 73104
5Department of Biochemistry and Molecular Biology, Center for
Tropical and Emerging Global Diseases, Complex Carbohydrate
Research Center, University of Georgia, Athens GA 30602
ϑCurrent address: Obstetrics and Gynecology (OBGYN),
1951 SW 172nd Ave, Hollywood, FL 33029
#Current address: York Biomedical Research Institute &
Department of Biology, University of York, Heslington,
York, YO10 5DD
§Current address: Chemistry Technology Center, Waters
Corporation, Milford, MA 01757
* Corresponding author: Christopher M. West
Glycobiology, accepted
O-GlcNAcylation is a prominent modification of nuclear and
cytoplasmic proteins in animals and plants, and is mediated by a
single O-GlcNAc transferase (OGT). Spindly (Spy), a paralog of
OGT first discovered in higher plants, has an ortholog in the
apicomplexan parasite Toxoplasma gondii, and both enzymes
are now recognized as O-fucosyltransferases (OFTs). Here we
investigate the evolution of spy-like genes and experimentally
confirm OFT activity in the social amoeba Dictyostelium – a protist
that is more related to fungi and metazoa. Immunofluorescence
probing with the fucose-specific Aleuria aurantia lectin (AAL) and
biochemical cell fractionation combined with western blotting
suggested the occurrence of nucleocytoplasmic fucosylation. The
absence of reactivity in mutants deleted in spy or gmd (unable to
synthesize GDP-Fuc) suggested monofucosylation mediated by
Spy. Genetic ablation of the modE locus, previously predicted to
encode a GDP-fucose transporter, confirmed its necessity for
fucosylation in the secretory pathway but not for the
nucleocytoplasmic proteins. Affinity capture of these proteins
combined with mass spectrometry confirmed monofucosylation
of Ser and Thr residues of several known nucleocytoplasmic
proteins. As in Toxoplasma, the Spy OFT was required for optimal
proliferation of Dictyostelium under laboratory conditions. These
findings support a new phylogenetic analysis of OGT and OFT
evolution that indicates their occurrence in the last eukaryotic
common ancestor but mostly complementary presence in its
eukaryotic descendants with the notable exception that both
occur in red algae and plants. Their generally exclusive
expression, high degree of conservation and shared
monoglycosylation targets suggest overlapping roles in
physiological regulation.
Submitted by Chris West [[log in to unmask]]
_________________________________________________________
Mining the chemodiversity of the plant genus myrica to reveal
bioactive molecules for their medicinal uses
This is a 4 year PhD studentship in interdisciplinary research, to
develop skills in natural product analytical chemistry, molecular
cell biology & pharmacology, focused on the characterisation of
medicinal natural products from the genus Myrica & identification
of related medicinal mechanisms.
Key words: cell biology, pharmacology, chemistry, agriculture,
medicines
Supervisors:
• Robin SB Williams, Royal Holloway University of London,
UK (RHUL)
• Melanie-Jayne Howes, Royal Botanic Gardens, Kew, UK
(RBGK)
• Phil Stevenson, Royal Botanic Gardens, Kew, UK (RBGK)
• Edna Makule, The Nelson Mandela African Institution of
Science & Technology, Tanzania
Weblink: Mining the chemodiversity of the plant genus Myrica to
reveal bioactive molecules for their medicinal uses
LIDo DTP (https://www.lido-dtp.ac.uk)
The World Health Organisation (WHO) recognises the importance
of Traditional Medicines (TMs) in many low-middle income
nations, where they are more affordable, accessible, and culturally
acceptable compared to conventional pharmaceuticals. However,
there is a knowledge gap to understand the scientific basis for the
use of many TMs, especially which are their bioactive molecules
and their mechanisms of action. In Tanzania the plant Myrica
salicifolia is a widely used TM but understanding the diversity of
its chemical constituents, and the molecular mechanisms of each
compound related to potential health and medicinal effects of
this TM remains to be defined.
This project aims to unlock the useful properties of the plant
genus Myrica by exploring the diversity of chemical traits and
bioactive molecules and their molecular functions to support
human health. This aim will be investigated through the following
interdisciplinary approach:
1. To build new understanding of the bioactive components
of Myrica species. The extensive plant Collections at Kew will be
sampled and analysed chemically to assess whether geography
or environment are determinants of medicinal plant chemistry.
2. To identify molecular mechanism(s) of Myrica bioactive
molecules to explain their current and potential medicinal uses.
The model D. discoideum will be employed to identify molecular
mechanisms and targets for the major constituents, with molecular
targets validated using in silico modelling and through rescue of
mutants by heterologous expression of human proteins.
This project will highlight the excellence of the combined research
approach from both RHUL and RBGK to provide new knowledge
regarding defined bioactive molecules, traits and diversity and
will propose molecular mechanisms for these molecules that
may underlie beneficial effects on health. Together, these
provide multidisciplinary training opportunities for the student
in established and complementary research environments to
improve our understanding and application of novel plant-
derived medicine.
The project is funded by the London Interdisciplinary Doctoral
Program and will be extremely competitive. Applications from UK
and international students are invited, with Masters or equivalent
qualifications and with an expectation of interest in developing
interdisciplinary skills. The student will work at both RBGK to
learn natural product and analytical chemistry skills, and at
RHUL to gain experience in cell and molecular biology and
pharmacology research.
This is a 4 year PhD studentship, with a stipend provided at a
standard UK rate. Closing date: 10 January 2023.
Starting date ~ Sept 2023.
For further details email Robin Williams ([log in to unmask])
Submitted by Robin Williams [[log in to unmask]]
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