There are a number of different types of cell membranes, ranging from the PM which separates the cell contents from the external environment to the internal membranes of subcellular organelles, such a mitochondria and the ER. Although the general lipid bilayer structure is similar in all membranes, they differ in their specific protein and lipid content and each type has its own specific features. No satisfactory scheme describing the assembly of any one of these membranes is currently available. Vesicular transport and the way in which various proteins are initially inserted into the membrane of the ER have been discussed earlier. Some general points about membrane assembly are addressed in the following discussion.

Asymmetry of Both Proteins & Lipids Is Maintained During Membrane Assembly

Vesicles formed from membranes of the ER and GA, either naturally or pinched off by homogenization, exhibit trans verse asymmetries of both lipid and protein. These asymmetries are maintained during fusion of transport vesicles with the PM. The inside of the vesicles after fusion becomes theoutside of the plasma membrane, and the cytoplasmic side of the vesicles remains the cytoplasmic side of the membrane (Figure 1). The enzymes responsible for the synthesis of phospholipids, the major class of lipids in membranes reside in the cytoplasmic surface of the cisternae (the sac-like structures) of the ER. Phospholipids are synthesized at that site, and it is thought that they self-assemble into thermodynamically stable bimolecular layers, thereby expanding the membrane and perhaps promoting the detachment of so-called lipid vesicles from it. It has been proposed that these vesicles travel to other sites, donating their lipids to other membranes. Phospholipid exchange proteins are cytosolic proteins that take up phospholipids from one membrane and release them to another are believed to play a role in regulating the specific lipid composition of various membranes.

Fig1. Fusion of a vesicle with the plasma mem brane 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. The lumen of a vesicle and the outside of the cell are topologically equivalent.

It should be noted that the lipid compositions of the ER, Golgi, and PM differ, the latter two membranes containing higher amounts of cholesterol, sphingomyelin, and glycosphingolipids, and less phosphoglycerides than does the ER. Sphingolipids pack more densely in membranes than do phosphoglycerides. These differences affect the structures and functions of membranes. For example, the thickness of the bilayer of the Golgi and plasma membrane is greater than that of the ER, which affects which particular transmembrane proteins are found in these organelles. Also, lipid rafts are believed to be formed in the Golgi.

Lipids & Proteins Undergo Turnover at Different Rates in Different Membranes

It has been shown that the half-lives of the lipids of the ER mem branes 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 widely, some exhibiting short (hours) and others long (days) half-lives. Thus, individual lipids and proteins of the ER mem branes appear to be inserted into it relatively independently and this is believed to be 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 modificationsthat membrane proteins may be subjected prior to attaining their mature state. These may include disulfide formation, proteolysis, assembly into multimers, glycosylation, addition of a glycophosphatidylinositol (GPI) anchor, sulfation on tyrosine or carbohydrate moieties, phosphorylation, acylation, and prenylation. Nevertheless, significant progress has been made; Table 1 summarizes some of the major features of membrane assembly that have emerged to date.

Table1. Some Major Features of Membrane Assembly

Various Disorders Result From Mutations in Genes Encoding Proteins Involved in Intracellular Transport

Some disorders reflecting abnormal peroxisomal function and abnormalities of protein synthesis in the ER and of the synthesis of lysosomal proteins have been listed earlier in this chapter. Many other mutations affecting folding of proteins and their intracellular transport to various organelles have been reported, including neurodegenerative disorders such as Alzheimer’s disease, Huntington’s disease, and Parkinson’s disease. The elucidation of the causes of these various conformational disorders has contributed significantly to our understanding of molecular pathology. The term“diseases of proteostasis deficiency” has also been applied to diseases due to misfolding of proteins. Proteostasis is a composite word derived from protein homeostasis. Normal proteostasis is due to a balance of many factors, such as synthesis, folding, trafficking, aggregation, and normal degradation. If any one of these is disturbed (eg, by mutation, aging, cell stress, or injury), a variety of disorders can occur, depending on the particular proteins involved.

Hsp90 is a chaperone protein which plays a part in the processing of 300 to 400 proteins, including some that are involved in cancer development, and it was identified as a target for antitumor therapy in the 1990s. A number of Hsp90 inhibitors have undergone clinical trials since then, but none so far have been approved for use by the FDA, mainly because of toxicity problems. The search for an Hsp90 inhibitor suit able for clinical use, however, is continuing. The chaperone Hsp70 is another potential anticancer target currently under investigation, since it is expressed much more strongly in tumor cells than in normal cells. Small drug molecules that act as chemical chaperones have also been shown to prevent misfolding and restore protein function.

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"مشروب محبوب" يخفي فوائد لا يعرفها كثيرون

طبيب يكشف 5 أنواع للسعال.. بعضها خطير

نقص فيتامينات "خفي".. قد يفسّر التعب والتنميل وقلة التركيز

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الآخبار التكنلوجية

دراسة: تغيّرات في أسلوب القيادة قد تكشف مبكرا عن الخرف !

عمرها 773 ألف سنة.. اكتشاف أقدم أحافير بشرية في المغرب

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مواضيع ذات صلة

Bone is Affected by many Metabolic & Genetic Disorders

Transport Vesicle Formation and Function Involves SNAREs & Other Factors

Misfolded Proteins Undergo Endoplasmic Reticulum Associated Degradation

Proteoglycans & Glycosaminoglycans

The ER Functions as The Quality Control Compartment of The Cell

Proteins Follow Several Routes to be Inserted Into or Attached to The Membranes of The Endoplasmic Reticulum

Proteins sorted via the Rough ER branch have N-Terminal signal peptides

Proteins Imported Into Peroxisomes Carry Unique Targeting Sequences

Transport of Macromolecules in & out of the Nucleus Involves Localization Signals

Most Mitochondrial Proteins Are Imported

Many proteins are targeted by signal sequences to their correct destinations

Conjugation reactions in phase 2 metabolism prepare Xenobiotics for excretion