A 60-Kilodalton Protein Component of the Counting Factor Complex Regulates Group Size in
            <i>Dictyostelium discoideum</i>

Brock, Debra A.; Egmond, Wouter N. van; Shamoo, Yousif; Hatton, R. Diane; Gomer, Richard H.

doi:10.1128/ec.00169-06

Cited by 17 publications

(19 citation statements)

References 39 publications

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“…As described below, all three of the rCfaD variants inhibit Dictyostelium cell proliferation, suggesting that CfaD acts as a signal despite its lack of detectable enzymatic activity. This is similar to what we had previously observed for two functional components of the Dictyostelium CF group size regulation signal, CF45-1 (which has similarity to lysozymes but no detectable lysozyme activity) and CF60 (which has similarity to acid phosphatases but little or no acid phosphatase activity) (Brock et al, 2003b; Brock et al, 2006). …”

Section: Resultssupporting

confidence: 89%

The secretedDictyosteliumprotein CfaD is a chalone

Bakthavatsalam

Brock

Nikravan

et al. 2008

Journal of Cell Science

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111

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Dictyostelium discoideum cells secrete CfaD, a protein that is similar to cathepsin proteases. Cells that lack cfaD proliferate faster and reach a higher stationary-phase density than wild-type cells, whereas cells that overexpress CfaD proliferate slowly and reach the stationary phase when at a low density. On a per-nucleus basis, CfaD affects proliferation but not growth. The drawback of not having CfaD is a reduced spore viability. Recombinant CfaD has no detectable protease activity but, when added to cells, inhibits the proliferation of wild-type and cfaD– cells. The secreted protein AprA also inhibits proliferation. AprA is necessary for the effect of CfaD on proliferation. Molecular-sieve chromatography indicates that in conditioned growth medium, the 60 kDa CfaD is part of a ∼150 kDa complex, and both chromatography and pull-down assays suggest that CfaD interacts with AprA. These results suggest that two interacting proteins may function together as a chalone signal in a negative feedback loop that slows Dictyostelium cell proliferation.

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Section: Resultssupporting

confidence: 89%

The secretedDictyosteliumprotein CfaD is a chalone

Bakthavatsalam

Brock

Nikravan

et al. 2008

Journal of Cell Science

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111

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“…CF60 is the fourth component of CF (Brock et al 2006). CF60 has some similarity to acid phosphatases, but recombinant CF60 has a very little or no phosphatase activity.…”

Section: Cf60mentioning

confidence: 99%

Combining experiments and modelling to understand size regulation inDictyostelium discoideum

Jang

Gomer

2008

J. R. Soc. Interface.

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Little is known about how the sizes of specific organs and tissues are regulated. To try to understand these mechanisms, we have been using a combination of modelling and experiments to study the simple system Dictyostelium discoideum, which forms approximately 20 000 cell groups. We found that cells secrete a factor, and as the number of cells increases, the concentration of the factor increases. Diffusion calculations indicated that this lets cells sense the local cell density. Computer simulations predicted, and experiments then showed, that this factor decreases cell-cell adhesion and increases random cell motility. In a group, adhesion forces keep cells together, while random motility forces cause cells to pull apart and separate from each other. As the group size increases above a threshold, the factor concentration goes above a threshold and the cells switch from an adhered state to a separated state. This causes excessively large groups to break apart and/or dissipate, creating an upper limit to group size. In this review, we focus on how computer simulations made testable predictions that led the way to understanding the size regulation mechanism mediated by this factor.

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“…Within an aggregation territory, excessively large streams break up into multiple groups, and this breakup is regulated by a secreted protein complex named counting factor (CF) (6)(7)(8)(9). Disrupting genes encoding CF components or adding antibodies against CF components prevents cells from sensing the presence of excessively large streams.…”

mentioning

confidence: 99%

“…Disrupting genes encoding CF components or adding antibodies against CF components prevents cells from sensing the presence of excessively large streams. The resulting unbroken streams merge into abnormally large aggregates (6)(7)(8)(9). Conversely, adding an excess amount of CF to developing wild-type cells results in excess stream breakup and thus small groups (6)(7)(8)(9)30).…”

mentioning

confidence: 99%

A Protein with Similarity to PTEN Regulates Aggregation Territory Size by Decreasing Cyclic AMP Pulse Size during Dictyostelium discoideum Development

Tang

Gomer

2008

Eukaryot Cell

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An interesting but largely unanswered biological question is how eukaryotic organisms regulate the size of multicellular tissues. During development, a lawn of Dictyostelium cells breaks up into territories, and within the territories the cells aggregate in dendritic streams to form groups of ϳ20,000 cells. Using random insertional mutagenesis to search for genes involved in group size regulation, we found that an insertion in the cnrN gene affects group size. Cells lacking CnrN (cnrN ؊ ) form abnormally small groups, which can be rescued by the expression of exogenous CnrN. Relayed pulses of extracellular cyclic AMP (cAMP) direct cells to aggregate by chemotaxis to form aggregation territories and streams. cnrN ؊ cells overaccumulate cAMP during development and form small territories. Decreasing the cAMP pulse size by treating cnrN ؊ cells with cAMP phosphodiesterase or starving cnrN ؊ cells at a low density rescues the small-territory phenotype. The predicted CnrN sequence has similarity to phosphatase and tensin homolog (PTEN), which in Dictyostelium inhibits cAMP-stimulated phosphatidylinositol 3-kinase signaling pathways. CnrN inhibits cAMP-stimulated phosphatidylinositol 3,4,5-trisphosphate accumulation, Akt activation, actin polymerization, and cAMP production. Our results suggest that CnrN is a protein with some similarities to PTEN and that it regulates cAMP signal transduction to regulate territory size.

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A 60-Kilodalton Protein Component of the Counting Factor Complex Regulates Group Size in Dictyostelium discoideum

Cited by 17 publications

References 39 publications

The secretedDictyosteliumprotein CfaD is a chalone

The secretedDictyosteliumprotein CfaD is a chalone

Combining experiments and modelling to understand size regulation inDictyostelium discoideum

A Protein with Similarity to PTEN Regulates Aggregation Territory Size by Decreasing Cyclic AMP Pulse Size during Dictyostelium discoideum Development

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