dictyNews
Electronic Edition
Volume 39, number 23
August 16, 2013

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Abstracts
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The cyclin-dependent kinase family in the social amoebozoan 
Dictyostelium discoideum

Robert J. Huber

Center for Human Genetic Research, Massachusetts General 
Hospital, Harvard Medical School, Richard B. Simches Research 
Center, 185 Cambridge Street, Boston, Massachusetts, USA 02114


Cellular and Molecular Life Sciences, in press

Cyclin-dependent kinases (Cdk) are a family of serine/threonine 
protein kinases that regulate eukaryotic cell cycle progression. 
Their ability to modulate the cell cycle has made them an attractive 
target for anti-cancer therapies. Cdk protein function has been 
studied in a variety of eukaryotes ranging from yeast to humans. 
In the social amoebozoan Dictyostelium discoideum several 
homologues of mammalian Cdks have been identified and 
characterized. The life cycle of this model organism is comprised 
of a feeding stage where single cells grow and divide mitotically as 
they feed on their bacterial food source and a multicellular 
developmental stage that is induced by starvation. Thus it is a 
valuable system for studying a variety of cellular and developmental 
processes. In this review I summarize the current knowledge of the 
Cdk protein family in Dictyostelium by highlighting the research 
efforts focused on the characterization of Cdk1, Cdk5, and Cdk8 in 
this model eukaryote. Accumulated evidence indicates that each 
protein performs distinct functions during the Dictyostelium life cycle 
with Cdk1 being required for growth and Cdk5 and Cdk8 being 
required for processes that occur during development. Recent 
studies have shown that Dictyostelium Cdk5 shares attributes with 
mammalian Cdk5 and that the mammalian Cdk inhibitor roscovitine 
can be used to inhibit Cdk5 activity in Dictyostelium. Together, these 
results show that Dictyostelium can be used as a model system for 
studying Cdk protein function.


Submitted by "Robert J.Huber" [[log in to unmask]]
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Loss of the Histidine Kinase DhkD Results in Mobile Mounds During 
Development of Dictyostelium discoideum.

Charles K. Singleton and Yanhua Xiong

Department of Biological Sciences, Vanderbilt University
VU Station B 351634, Nashville, TN 37235-1634


PLOS ONE, in press

Background.  Histidine kinases are receptors for sensing cellular and 
environmental signals, and in response to the appropriate cue they 
initiate phosphorelays that regulate the activity of response regulators.  
The Dictyostelium discoideum genome encodes 15 histidine kinases 
that function to regulate several processes during the multicellular 
developmental program, including the slug to culmination transition, 
osmoregulation, and spore differentiation.  While there are many 
histidine kinases, there is only a single response regulator, RegA.  
Not surprisingly given the ubiquitous involvement of cAMP in 
numerous processes of development in Dictyostelium, RegA is a 
cAMP phosphodiesterase that is activated upon receiving phosphates 
through a phosphorelay.  Hence, all of the histidine kinases 
characterized to date regulate developmental processes through 
modulating cAMP production.  Here we investigate the function of 
the histidine kinase DhkD.

Principal Findings.  The dhkD gene was disrupted, and the resulting 
cells when developed gave a novel phenotype.  Upon aggregation, 
which occurred without streaming, the mounds were motile, a 
phenotype termed the pollywog stage.  The pollywog phenotype was 
dependent on a functional RegA.  After a period of random migration, 
the pollywogs attempted to form fingers but mostly generated aberrant 
structures with no tips.  While prestalk and prespore cell differentiation 
occurred with normal timing, proper patterning did not occur. In contrast, 
wild type mounds are not motile, and the cAMP chemotactic movement 
of cells within the mound facilitates proper prestalk and prespore 
patterning, tip formation, and the vertical elongation of the mound 
into a finger.

Conclusions.  We postulate that DhkD functions to ensure the proper 
cAMP distribution within mounds that in turn results in patterning, tip 
formation and the transition of mounds to fingers.  In the absence of 
DhkD, aberrant cell movements in response to an altered cAMP 
distribution result in mound migration, a lack of proper patterning, and 
an inability to generate normal finger morphology.


Submitted by Charles Singleton [[log in to unmask]]
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[End dictyNews, volume 39, number 23]