Cell News | Issue 01, 2017 - page 35

Cell News 01/2017
A MORN repeat protein directly binds PI(4,5)P2 and
is essential for cell viability in trypanosomes
Sara Sajko, Kristina Djinovic-Carugo, Brooke Morriswood
Presenting author: Brooke Morriswood
Department of Cell & Developmental Biology (Zoology 1),
Biocenter, University of Würzburg, Würzburg, Germany
Membrane occupation and recognition nexus (MORN) re-
peats are 23-amino acid motifs that are found in proteins
throughout the tree of life. Each repeat is predicted to form a
beta-hairpin structure, and arrays of these repeats are found
in conjunction with a wide variety of protein architectures.
One of the best known are the junctophilin family of proteins
that are key components of junctional membrane complexes in
excitatory cells, responsible for linking the plasma membrane
to an intracellular membrane such as the endoplasmic reticu-
lum. MORN repeat proteins are relatively poorly-characterised
at a cell biology level however, and the exact function of the
repeats is unclear. The MORN1 protein in the early-branch-
ing eukaryote Trypanosoma brucei is composed solely of 15
tandem MORN repeats, and therefore represents an excellent
system in which to probe the function(s) of MORN repeats
in general. TbMORN1 is found in a hook-shaped cytoskele-
tal complex that is looped around the neck of the flagellar
pocket, an invagination of the plasma membrane that is the
sole site of endo- and exocytic traffic. Depletion of TbMORN1
is rapidly lethal, and results in an enlargement of the flagellar
pocket and indications of impaired macromolecule uptake. In
vitro studies with recombinant TbMORN1 indicate that it can
directly interact with the phospholipid PI(4,5)P2, an endocytic
effector. This is the first indication that MORN repeats are
capable of direct interactions with phospholipids.
Drosophila WASH is required for integrin-mediated cell
adhesion, cell motility and lysosomal neutralization
Nagel BM, Bechtold M, Rodriguez LG, Bogdan S
Presenting author: Benedikt Nagel
Institut für Neurobiologie, Universität Münster, Badestr. 9,
48149 Münster, Germany
The Wiskott-Aldrich syndrome protein and SCAR homolog
(WASH; also known as Washout in flies) is a conserved ac-
tin-nucleation-promoting factor controlling Arp2/3 complex
activity in endosomal sorting and recycling. Previous studies
have identified WASH as an essential regulator in Drosophila
development. Here, we show that homozygous wash mutant
flies are viable and fertile. We demonstrate that Drosophila
WASH has conserved functions in integrin receptor recycling
and lysosome neutralization. WASH generates actin patches on
endosomes and lysosomes, thereby mediating both aforemen-
tioned functions. Consistently, loss of WASH function results
in cell spreading and cell migration defects of macrophages,
and an increased lysosomal acidification that affects effi-
cient phagocytic and autophagic clearance. WASH physically
interacts with the vacuolar (V)-ATPase subunit Vha55 that is
crucial to establish and maintain lysosome acidification. As a
consequence, starved flies that lack WASH function show a
dramatic increase in acidic autolysosomes, causing a reduced
lifespan. Thus, our data highlight a conserved role for WASH
in the endocytic sorting and recycling of membrane proteins,
such as integrins and the V-ATPase, that increase the likelihood
of survival under nutrient deprivation.
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