Increased amounts of HMG-CoA reductase induce "karmellae": a proliferation of stacked membrane pairs surrounding the yeast nucleus.

Abstract

Abstract. Overproduction of the enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase in yeast resulted in striking morphological effects on the structure of intracellular membranes. Specifically, stacks of paired membranes closely associated with the nuclear envelope were observed in strains that overproduced the HMG1 isozyme, one of two isozymes for HMG-CoA reductase in yeast. These nuclear-associated, paired membranes have been named "karmellae" In strains that overproduced the HMG1 isozyme, HMG-CoA reductase was present in the karmellar layers. At mitosis, karmellae were asymmetrically segregated: the mother cells inherited all of the karmellae and the daughter cells inherited none. A membranous structure of different morphology was occasionally found in cells that overproduced the HMG2 isozyme. These observations further establish the existence of cellular mechanisms that monitor the levels of membrane proteins and compensate for changes in these levels by inducing synthesis of particular types of membrane.

Proliferation of the endoplasmic reticulum occurs normally in cells that lack a functional unfolded protein response

“…(Koning et al, 1993(Koning et al, , 1996Profant et al, 2000;Wright et al, 1988) The lack of a growth assay has slowed searches for genes involved in karmellae assembly, since the only way to detect their presence is by direct microscopic examination. The discovery of a strain background (ire1) in which the presence of karmellae conferred a death phenotype was extremely exciting to us (Cox et al, 1997).…”

“…In the JRY527 wild-type background, karmellae are present in about 30-60% of the cells, depending on the promoter used to express Hmg1p. The bulk of this heterogeneity is believed to reflect asymmetry of karmellae segregation at mitosis: the mother cell retains the karmellae membranes and the daughter cell inherits a normal nuclear envelope/ER (Wright et al, 1988). Therefore it is necessary to count Figure 5.…”

“…A dramatic example of regulation of organelle biogenesis involves the proliferation of ER arrays in response to increased expression of certain ER membrane proteins (Naik and Jones, 1998;Nishikawa et al, 1994;Schunck et al, 1991;Vergeres et al, 1993;Wanker et al, 1995;Wright et al, 1988). When the level of the sterolbiosynthetic enzyme, HMG-CoA reductase, is elevated experimentally or by treatment with drugs (Singer et al, 1988), cells assemble novel arrays of smooth ER.…”

“…In mammals, the ER proliferations form hexagonal arrays of smooth membrane tubules known as crystalloid ER (Anderson et al, 1983;Chin et al, 1982). In yeast, the ER proliferations consist of stacked cisternae known as karmellae, which are closely associated with the nucleus (Wright et al, 1988) or can be present in the cytoplasm (Koning et al, 1996). Karmellae and similar ER proliferations provide a useful experimental system for discovering the molecular mechanisms that enable cells to adjust organelle quantity and quality according to physiological demands.…”

The role of lipids in the biogenesis of integral membrane proteins

“…The colocalization of these two process is likely not incidental but a means to ensure the balanced growth of both lipid and protein constituents of a membrane. Striking examples of this coordination are observed upon overexpression of integral membrane proteins, which results in the induction of surplus membranes to accommodate the overexpressed protein (Wright et al 1988). Lipids, however, are also more directly implicated in the membrane insertion and translocation process, as many of the components of the assembly machinery are known to be lipid-dependent.…”