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Regulatory peptides in protozoons?

Thu Feb 8 19:10:31 EST 1996

 Morty at biochem.unp.ac.za (Rory.Morty) wrote:

>Subject:       Regulatory peptides in protozoons?
>Date:          Thu, 8 Feb 1996 13:36:15 GMT
>Hi all,
>Is anybody aware of any literature reporting the presence of regulatory 
>peptides in protozoons? I would appreciate it if you would e-mail me.
>Many thank's in advance,
>Rory Morty
>e-mail: morty at bchm.unp.ac.za

A range of factors that sense cell density have been decribed in the cellular slime 
mould Dictyosteium discoideum.  Some fragments out of a review I am writing:

The earliest starvation induced promoters are termed the "prestarvation response" 
(Clarke et al., 1987, 1988) and are controlled by both the cells nutritional status 
and an extracellular "prestarvation factor" (PSF).  PSF is an autocrine signal 
secreted by growing cells that accumulates in the medium in proportion to cell density 
(Rathi et al., 1991; Rathi and Clarke, 1992).  Cells grown on bacteria only respond to 
PSF when the bacteria become depleted, inducing the prestarvation genes about three 
generations before the cells cease logarithmic growth (Clarke et al., 1987). 

PSF also induces the production of a range of proteins required for the early stages 
of multicellular development, eg contact sites B EDTA sensitive adhesion protein 
(Rathi and Clarke, 1992).  PSF is produced by growing cells and production decreases 
in starvation to low lvevels by 4 hours.  Thus, PSF will be in excess under the high 
cell concentrations (>5x106) used for the production of recombinant proteins unless 
the starving cells are washed.  PSF is a heat labile, non-dialysable glycoprotein 
protein which binds to the lectin ConA (Rathi and Clarke, 1992).  Note that the PSF 
does not inhibit cell growth (Clarke et al. 1988).  However, stationary phase cells 
produce other factors which if added to log phase cells will block cell division and 
depress the rate of transcription, but which do not affect transcription in stationary 
phase cells (Yarger et al., 1974; Yarger and Soll, 1975; Soll et al., 1976; Ferguson 
and Soll, 1976).  These growth inhibitory factors provide an explanation of why most 
D. discoideum  cultures stop growing at around 1-2x107 cells per ml in the presence of 
excess nutrients, but their effects on the transcription of prestarvation genes is 
unclear.  Axenically grown, stationary phase cells (1x107/ml) no longer express the 
prestarvation gene discoidin I (Devine et al, 1982).

Expression of developmentally regulated genes  requires a second cell density sensing 
signal "conditioned medium factor" (CMF) which is different to PSF described above 
(Clarke et al., 1992), although CMF also causes elevated expression of discoidin I in 
starving cells  (Gomer et al., 1991).  CMF's function is to ensure that multicellular 
development only occurs above a threshold cell density.  CSF is slowly secreted by 
starving cells  and the extracellular levels signals the cell density.  Although CSF 
does not appear to be secreted by growing cells (Gomer et al., 1991), it is present in 
internal vesicles (Yuen et al., 1991).  The receptor for CMF is virtually absent from 
growing cells and is maximally expressed in cells starved for 6-8 hours (Jain and 
Gomer, 1994).  CMF is an 80 kDa protease sensitive glycoprotein (Gomer et al, 1991; 
Jain et al., 1992), but after 10 hours of starvation, proteolytic break down of CMF 
produces 0.5-6.5 kDa glycopeptides which are 100 fold more active than the intact 
molecule (Yuan et al., 1991). 

Best wishes, 
Martin Slade,
School of Biological Sciences,
Macquarie University,
NSW 2109,
FAX  (61 2) 850 8174
Phone(61 2) 850 8210

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