Lipids Proteins Undergo Turnover at Different Rates in Different Membranes

It has been shown that the half-lives of the lipids of the ER membranes of rat liver are generally shorter than those of its proteins, so that the turnover rates of lipids and proteins are independent. Indeed, different lipids have been found to have different half-lives. Furthermore, the half-lives of the proteins of these membranes vary quite widely, some exhibiting short (hours) and others long (days) half-lives. Thus, individual lipids and proteins of the ER membranes appear to be inserted into it relatively independently; this is the case for many other membranes.

The biogenesis of membranes is thus a complex process about which much remains to be learned. One indication of the complexity involved is to consider the number of posttranslational modifications that membrane proteins may be subjected to prior to attaining their mature state. These include proteolysis, assembly

Membrane protein

Exterior surface

Membrane protein

Exterior surface

Plasma membrane

Integral protein

Vesicle membrane

Plasma membrane

Integral protein

Vesicle membrane

Figure 46-8. Fusion of a vesicle with the plasma membrane preserves the orientation of any integral proteins embedded in the vesicle bilayer. Initially, the amino terminal of the protein faces the lumen, or inner cavity, of such a vesicle. After fusion, the amino terminal is on the exterior surface of the plasma membrane. That the orientation of the protein has not been reversed can be perceived by noting that the other end of the molecule, the carboxyl terminal, is always immersed in the cytoplasm. The lumen of a vesicle and the outside of the cell are topologically equivalent. (Redrawn and modified, with permission, from Lodish HF, Rothman JE: The assembly of cell membranes. Sci Am [Jan] 1979;240:43.)

Figure 46-8. Fusion of a vesicle with the plasma membrane preserves the orientation of any integral proteins embedded in the vesicle bilayer. Initially, the amino terminal of the protein faces the lumen, or inner cavity, of such a vesicle. After fusion, the amino terminal is on the exterior surface of the plasma membrane. That the orientation of the protein has not been reversed can be perceived by noting that the other end of the molecule, the carboxyl terminal, is always immersed in the cytoplasm. The lumen of a vesicle and the outside of the cell are topologically equivalent. (Redrawn and modified, with permission, from Lodish HF, Rothman JE: The assembly of cell membranes. Sci Am [Jan] 1979;240:43.)

Table 46-8. Major features of membrane assembly.

• Lipids and proteins are inserted independently into membranes.

• Individual membrane lipids and proteins turn over independently and at different rates.

• Topogenic sequences (eg, signal [amino terminal or internal] and stop-transfer) are important in determining the insertion and disposition of proteins in membranes.

• Membrane proteins inside transport vesicles bud off the endoplasmic reticulum on their way to the Golgi; final sorting of many membrane proteins occurs in the trans-Golgi network.

• Specific sorting sequences guide proteins to particular organelles such as lysosomes, peroxisomes, and mitochondria.

into multimers, glycosylation, addition of a glycophos-phatidylinositol (GPI) anchor, sulfation on tyrosine or carbohydrate moieties, phosphorylation, acylation, and prenylation—a list that is undoubtedly not complete. Nevertheless, significant progress has been made; Table 46-8 summarizes some of the major features of membrane assembly that have emerged to date.

Table 46-9. Some disorders due to mutations in genes encoding proteins involved in intracellular membrane transport.1

Disorder2

Protein Involved

Chédiak-Higashi syndrome, 214500

Lysosomal trafficking regulator

Combined deficiency of factors V and VIII, 227300

ERGIC-53, a mannose-binding lectin

Hermansky-Pudlak syndrome, 203300

AP-3 adaptor complex P3A subunit

I-cell disease, 252500

N-Acetylglucosamine 1-phosphotransferase

Oculocerebrorenal syndrome, 30900

OCRL-1, an inositol polyphosphate 5-phosphatase

1Modified from Olkonnen VM, Ikonen E: Genetic defects of intra-cellular-membrane transport. N Eng J Med 2000;343:1095. Certain related conditions not listed here are also described in this publication. I-cell disease is described in Chapter 47. The majority of the disorders listed above affect lysosomal function; readers should consult a textbook of medicine for information on the clinical manifestations of these conditions.

2The numbers after each disorder are the OMIM numbers.

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