dictyNews
Electronic Edition
Volume 49, number 21
August 25, 2023
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Abstracts
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Synergy between a cytoplasmic vWFA/VIT protein and a
WD40-repeat F-box protein controls development in Dictyostelium
Andrew W. Boland1,2,5, Elisabet Gas-Pascual1,2,3, Hanke van
der Wel1, Hyun W. Kim1, Christopher M. West1,2,3,4
1Dept. of Biochemistry & Molecular Biology,
2Complex Carbohydrate Research Center,
3Center for Tropical and Emerging Global Diseases, University of
Georgia, Athens, GA 30602
4 to whom requests for information or materials should be sent:
Dept. of Biochemistry & Molecular Biology, 120 E. Green St., Davison
Life Sciences – B129, University of Georgia, Athens GA 30602 USA,
telephone +1-706-542-4259, email [log in to unmask]
5 current address: 10 Bromfield Street, Watertown MA 02472
Frontiers in Cell and Developmental Biology, Section Morphogenesis
and Patterning – accepted for publication
Like most eukaryotes, the pre-metazoan social amoeba Dictyostelium
depends on the SCF (Skp1/cullin-1/F-box protein) family of E3 ubiquitin
ligases to regulate its proteome. In Dictyostelium, starvation induces a
transition from unicellular feeding to a multicellular slug that responds
to external signals to culminate into a fruiting body containing terminally
differentiated stalk and spore cells. These transitions are subject to
regulation by F-box proteins and O2-dependent posttranslational
modifications of Skp1. Here we examine in greater depth the essential
role of FbxwD and Vwa1, an intracellular vault protein inter-alpha-trypsin
(VIT) and von Willebrand factor-A (vWFA) domain containing protein
that was found in the FbxwD interactome by co-immunoprecipitation.
Reciprocal co-IPs using gene-tagged strains confirmed the interaction
and similar changes in protein levels during multicellular development
suggested co-functioning. FbxwD overexpression and proteasome
inhibitors did not affect Vwa1 levels suggesting a non-substrate
relationship. Forced FbxwD overexpression in slug tip cells where it
is normally enriched interfered with terminal cell differentiation by a
mechanism that depended on its F-box and RING domains, and on
Vwa1 expression itself. Whereas vwa1-disruption alone did not affect
development, overexpression of either of its three conserved domains
arrested development but the effect depended on Vwa1 expression.
Based on structure predictions, we propose that the Vwa1 domains
exert their negative effect by artificially activating Vwa1 from an
autoinhibited state, which in turn imbalances its synergistic function
with FbxwD. Autoinhibition or homodimerization might be relevant
to the poorly understood tumor suppressor role of the evolutionarily
related VWA5A/BCSC-1 in humans.
Submitted by Chris West ([log in to unmask])
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[End dictyNews, volume 49, number 21]
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