Cell volume/proliferation, regulation

CaSR may also influence the proliferative and apoptotic status of the cells indirectly via modulation of cell volume homeostasis. Indeed, stimulation of CaSR in human epithelial cells induces upregulation of volume-regulated anion channels (VRAC) via a G protein-mediated increase in intracellular cAMP (Shimizu, et al., 2000). Proliferation and apoptosis are associated with essential volume perturbations [e.g., (Lang, et al., 2000)] and VRAC, a key component of homeostatic volume regulation, has been directly implicated in proliferation (Chen, et al., 2002, Doroshenko, et al., 2001, Shen, et al., 2000, Wang, et al., 2002) and apoptosis (Lemonnier, et al., 2004, Okada, et al., 2001, Okada, et al., 2006, Shen, et al., 2002). Consequently, extracellular Ca2+ may affect carcinogenesis via the CaSR-VRAC-cell volume links. The Ca2+ -permeable store-operated channel (SOC) is directly and functionally coupled to VRAC in an androgen-dependent LNCaP human prostate cancer epithelial cell line (Lemonnier, et al., 2002), evidence for another, CaSR-unrelated, potential mechanism for extracellular Ca2+ involvement in proliferative and apoptotic events. 

Lang, F., Ritter, M., Gamper, N., Huber, S., Fillon, S., Tanneur, V., Lepple-Wienhues, A., Szabo, I. and Gulbins, E., 2000, Cell volume in the regulation of cell proliferation and apoptotic cell death. Cell Physiol Biochem 10, 417-28. 

In contrast to Xenopus laevis, the maternal histone pool in the mouse one-cell embryo (based on synthetic rates for histones) is probably sufficient for only one to two rounds of DNA replication (Wassarman and Mrozak, 1981). Consistent with such a small histone pool is the observation that poly spermic eggs have the capacity to transform up to three to four sperm nuclei into metaphase chromosomes (Clarke and Masui, 1986) a similar capacity was also determined from experiments that manipulated the cytoplasmic volume by either bisection or cell fusion (Clarke and Masui, 1987). This small pool of maternal histones may hence be insufficient to prevent effectively the assembly of stable basal transcription complexes. Thus, titration of the maternal histone pool by an increase in the mass of DNA due to blasto-mere proliferation may not be a critical factor in regulating the onset of transcription in the mouse embryo and other mammalian eggs this is because the maternal transcription factors may be able to outcompete successfully maternal histones for the newly replicated chromatin. This could, at least in part, account for the early onset of transcription in mammalian embryos ranging from rodents to humans (Telford et al., 1990). Moreover, the lack of arapid S phase in the mouse embryo and other mammalian embryos would permit sufficient time for productively assembled transcription complexes to generate full-length transcripts. In contrast to mammalian embryos, S phase is very short prior to the midblastula transition in Xenopus laevis (Newport and Kirschner, 1982) and hence these rapid rounds of DNA replication could prematurely terminate the transcription of genes for which transcription had initiated. 

Plasma membranes of all cells investigated so far contain an electron transport system transferring electrons from NADH to an extracellular electron acceptor (for review, see Navas et al., 1994 and Chapter 4 of this volume). Electron transport across the plasma membrane is accompanied by release of protons from the cell, presumably due to an activation of the Na+/H+ antiport (Sun et a/., 1988). Since proton release and the concomitant increase in cytoplasmic pH have been connected to growth stimulation (Moolenar et al., 1983), it was proposed that the transplasma membrane redox system via proton release might also be involved in the regulation of proliferation. 

Determination of competent tissues and inductors as well as differentiation occur at the same time as cell proliferation. This proliferation not only forms cell clones but also significantly regulates their interactions. Through proliferation, the cellular and tissue levels are related with each other. Actually, early embryogenesis is characterized by the formation and interaction of cell masses of certain volumes. These volumes are dependent upon different rates of cell division. In turn, DNA replication differs in various differentiating systems. 

---