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dictyNews Volume 40 Number 24
dictyNews
Electronic Edition
Volume 40, number 24
September 19, 2014
Please submit abstracts of your papers as soon as they have been
accepted for publication by sending them to dicty@northwestern.edu
or by using the form at
http://dictybase.org/db/cgi-bin/dictyBase/abstract_submit.
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Abstracts
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PTEN Hopping on the Cell Membrane Is Regulated via a
Positively-Charged C2 Domain
Masato Yasui, Satomi Matsuoka, Masahiro Ueda
PLoS Computational Biology, 10(9): e1003817.
PTEN, a tumor suppressor that is frequently mutated in a wide spectrum
of cancers, exerts PI(3,4,5)P3 phosphatase activities that are regulated
by its dynamic shuttling between the membrane and cytoplasm. Direct
observation of PTEN in the interfacial environment can offer
quantitative information about the shuttling dynamics, but remains
elusive. Here we show that positively charged residues located in the
Calpha2 helix of the C2 domain are necessary for the membrane localization
of PTEN via stable electrostatic interactions in Dictyostelium discoideum.
Single-molecule imaging analyses revealed that PTEN molecules moved
distances much larger than expected had they been caused by lateral
diffusion, a phenomenon we call "hopping." Our novel single-particle
tracking analysis method found that the Calpha2 helix aids in regulating
the hopping and stable-binding states. The dynamically established
membrane localization of PTEN was revealed to be essential for
developmental processes and clarified a fundamental regulation mechanism
of the protein quantity and activity on the plasma membrane.
Submitted by Satomi Matsuoka [s.matsuoka@riken.jp]
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Loss of Cln3 function in the social amoeba Dictyostelium discoideum
causes pleiotropic effects that are rescued by human CLN3
Robert J. Huber*, Michael A. Myre , Susan L. Cotman
Center for Human Genetic Research, Massachusetts
General Hospital, Harvard Medical School,
185 Cambridge Street, Boston, Massachusetts, USA 02114
* Corresponding author
These authors contributed equally to the work
PLoS One, accepted
The neuronal ceroid lipofuscinoses (NCL) are a group of inherited,
severe neurodegenerative disorders also known as Batten disease.
Juvenile NCL (JNCL) is caused by recessive loss-of-function
mutations in CLN3, which encodes a transmembrane protein that
regulates endocytic pathway trafficking, though its primary
function is not yet known. The social amoeba Dictyostelium
discoideum is increasingly utilized for neurological disease
research and is particularly suited for investigation of protein
function in trafficking. Therefore, here we establish new
overexpression and knockout Dictyostelium cell lines for JNCL
research. Dictyostelium Cln3 fused to GFP localized to the
contractile vacuole system and to compartments of the endocytic
pathway. cln3- cells displayed increased rates of proliferation
and an associated reduction in the extracellular levels and
cleavage of the autocrine proliferation repressor, AprA. Mid-
and late development of cln3- cells was precocious and cln3-
slugs displayed increased migration. Expression of either
Dictyostelium Cln3 or human CLN3 in cln3- cells suppressed the
precocious development and aberrant slug migration, which were
also suppressed by calcium chelation. Taken together, our
results show that Cln3 is a pleiotropic protein that negatively
regulates proliferation and development in Dictyostelium. This
new model system, which allows for the study of Cln3 function
in both single cells and a multicellular organism, together with
the observation that expression of human CLN3 restores
abnormalities in Dictyostelium cln3- cells, strongly supports
the use of this new model for JNCL research.
Submitted by Robert Huber [rhuber@mgh.harvard.edu]
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[End dictyNews, volume 40, number 24]
