Regulation and processing of a secreted protein that mediates sensing of cell density in <i>Dictyostelium</i>

Yuen, Ita S.; Taphouse, Carl Richard; Halfant, K.A.; Gomer, Richard H.

doi:10.1242/dev.113.4.1375

Cited by 35 publications

(1 citation statement)

References 42 publications

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“…During growth, loss of cln3 reduces the extracellular amount of conditioned medium factor A (CmfA) ( Huber, 2017 ) ( Fig. 3 ), a glycoprotein that enables starving cells to respond to pulses of cAMP ( Yuen et al, 1991 ). These findings, coupled with the effect of cln3 deficiency on AprA secretion and cleavage during growth, suggest that the delayed aggregation is due to cln3 − cells not being primed to enter the developmental program owing to alterations in cell–cell signaling.…”

Section: Cln3 Deficiency Affects Adhesion and Aggregation Of D Discoideum Through Protein Secretionmentioning

confidence: 99%

Altered protein secretion in Batten disease

Huber

2021

Disease Models &Amp; Mechanisms

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The neuronal ceroid lipofuscinoses (NCLs), collectively known as Batten disease, are a group of neurological diseases that affect all ages and ethnicities worldwide. There are 13 different subtypes of NCL, each caused by a mutation in a distinct gene. The NCLs are characterized by the accumulation of undigestible lipids and proteins in various cell types. This leads to progressive neurodegeneration and clinical symptoms including vision loss, progressive motor and cognitive decline, seizures, and premature death. These diseases have commonly been characterized by lysosomal defects leading to the accumulation of undigestible material but further research on the NCLs suggests that altered protein secretion may also play an important role. This has been strengthened by recent work in biomedical model organisms, including Dictyostelium discoideum, mice, and sheep. Research in D. discoideum has reported the extracellular localization of some NCL-related proteins and the effects of NCL-related gene loss on protein secretion during unicellular growth and multicellular development. Aberrant protein secretion has also been observed in mammalian models of NCL, which has allowed examination of patient-derived cerebrospinal fluid and urine for potential diagnostic and prognostic biomarkers. Accumulated evidence links seven of the 13 known NCL-related genes to protein secretion, suggesting that altered secretion is a common hallmark of multiple NCL subtypes. This Review highlights the impact of altered protein secretion in the NCLs, identifies potential biomarkers of interest and suggests that future work in this area can provide new therapeutic insight.

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Section: Cln3 Deficiency Affects Adhesion and Aggregation Of D Discoideum Through Protein Secretionmentioning

confidence: 99%

Altered protein secretion in Batten disease

Huber

2021

Disease Models &Amp; Mechanisms

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Phosphorylation of the G protein α-subunit, Gα2, ofDictyostelium discoideum requires a functional and activated Gα2

Gundersen

1997

J. Cell. Biochem.

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The G alpha 2-subunit of Dictyostelium discoideum is essential to the initial stage of the cell's developmental life cycle. In response to the extracellular chemoattractant, cAMP, G alpha 2 is activated and transiently phosphorylated on serine-113 [Chen et al. (1994): J Biol Chem 269:20925-20930]. The role of G alpha 2 phosphorylation remains elusive; cells expressing the S113A, nonphosphorylated mutation of G alpha 2 appear to proceed through the developmental phase normally. To gain insight into the function of G alpha 2 phosphorylation, the conditions for G alpha 2 phosphorylation were examined using a variety of alpha-subunit point mutations and chimeras. Mutations that block the G protein activation cycle prior to or at the hydrolysis of GTP (G alpha 2-S45A, G alpha 2-G207A, and G alpha 2-Q208L) preclude G alpha 2 phosphorylation in vivo. Phosphorylation of the G alpha 2-Q208L mutation does however occur in an in vitro phosphorylation assay. It appears that G alpha 2 phosphorylation, shown previously in vivo to require the cAMP receptor, also requires signaling through the G2 pathway. Results from the in vitro assay suggest that the substrate for phosphorylation is the alpha-subunit monomer.

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PSF and CMF, autocrine factors that regulate gene expression during growth and early development ofDictyostelium

1995

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Throughout growth and development, Dictyostelium cells secrete autocrine factors that accumulate in proportion to cell density. At sufficient concentration, these factors cause changes in gene expression. Vegetative Dictyostelium cells continuously secrete prestarvation factor (PSF). The bacteria upon which the cells feed inhibit their response to PSF, allowing the cells to monitor their own density in relation to that of their food supply. At high PSF/bacteria ratios, which occur during late exponential growth, PSF induces the expression of several genes whose products are needed for cell aggregation. When the food supply has been depleted, PSF production declines, and a second density-sensing pathway is activated. Starving cells secrete conditioned medium factor (CMF), a glycoprotein of Mr 80 kDa that is essential for the development of differentiated cell types. Antisense mutagenesis has shown that cells lacking CMF cannot aggregate, and preliminary data suggest that CMF regulates cAMP signal transduction. Calculations indicate that a mechanism of simultaneously secreting and recognizing a signal molecule, as used by Dictyostelium to monitor cell density, could also be used to determine the total number of cells in a tissue.

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Regulation and processing of a secreted protein that mediates sensing of cell density in Dictyostelium

Cited by 35 publications

References 42 publications

Altered protein secretion in Batten disease

Altered protein secretion in Batten disease

Phosphorylation of the G protein α-subunit, Gα2, ofDictyostelium discoideum requires a functional and activated Gα2

PSF and CMF, autocrine factors that regulate gene expression during growth and early development ofDictyostelium

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