Membrane proteins permeabilized membranes formed

TABLE 11.2 Permeabilized Membranes Formed by Inserting Membrane Proteins and Biopores ... 

Another bio-inspired approach is to design polymersomes as enclosed reaction compartments for the development of nanoreactors, nanodevices, or artificial organelles, in which active compounds are not only protected from the environment, but also allowed to act in situ. For such function, membrane permeability is of crucial importance, since it allows the exchange of substrates/products with the environment of the pol)maersomes. Various methods have been reported to generate polymersomes with permeable membranes (i) polymers forming intrinsically porous membranes, (ii) polymer membranes that are permeable to ions as e.g. specific oxygen species, (iii) pore formation in pH responsive polymer membranes by chemical treatment, (iv) polymer membrane permeabilization by UV-irradiation, and (v) biopores or membrane proteins inserted into polymer membranes. ... 

Following the outer mitochondrial membrane permeabilization, the apoptogenic factors are released into the cytoplasm. Among them, cytochrome c has an important role in caspase activation, because it is the cofactor for assembling a large caspase 9 activating complex in the cytoplasm, called apoptosome. Along with cytochrome c, the Apaf-1 protein and dATP or ATP are required to form this complex in the cytoplasm (Hill et al., 2003). 

Structural homologies between PFTs and other toxins have not been identified. However, the process of membrane permeabilization may be operative in many cases where proteins have to escape from an intracellular compartment. Well known examples are diphtheria toxin, the neurotoxins and anthrax toxin. Specific domains in many intracel-lularly active toxins have in fact been shown to produce pores in artificial lipid bilayers, and membrane permeabilization is thought to form the basis for translocation of the active moieties from the late endo-some to the cytoplasm (reviewed in Montecucco et ai, 1994). The molecular mechanism of this translocation remains obscure. In the... 

A large body of literature describes the occurrence of pores, of various sizes and lifetimes, as the result of electroporation. In uiuo these pores may not necessarily be neatly rounded structures, but rather a mixture of shapes of permeabilization structures depending on the effect of transmembrane protein domains, cell shape, and surrounding matrix on the cell membrane response to the field, i.e. these permeabilizahon structures could either be circular in form, or have other forms depending on local factors. 

Alzheimer s, Parkinson s and prion diseases are characterized by neuronal loss and protein aggregates that may or may not be fibrillar. However, the exact identity of the neurotoxic species and the mechanism by which it kills neurons are unknown. Biophysical studies support the emerging notion that a prefibrillar oligomer (protofibril) may be responsible for cell death and that the fibrillar form that is typically observed post mortem may actually be neuroprotective. The laboratory of Peter Lansbury suggests that a subpopulation of the soluble protofibrils may function as pathogenic pores that might have the ability to permeabilize cell or mitochondrial membranes 35). Annular, pore-like structures are observed in familial mutants of a-synuclein (Parkinson s disease) and Alzheimer s precursor protein (Alzheimer s disease) as shown in Plate 3A 56). 

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