Moss - What genes cant do - 2003 (522929), страница 22
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Of82Chapter 3the four categories of possible protein destinations mentioned above,three of them require transit through the membrane system.Proteins which will remain resident in any membrane, which willremain resident in the lumen of any membranous body, or which will beexcreted into the extracellular milieu all enter the membrane system atthe same port of entry, the endoplasmic reticulum (ER). Membrane lipidstoo are synthesized at the ER, so the flow of biosynthetically new materials in the membrane system is vectorally directed outward, i.e., fromthe most central membranous body radially outward through each successive pancake in the stack and toward the plasma membrane.Protein synthesis is initiated in the cytosol of the cell when a messenger RNA molecule has passed through the nuclear pore and has triggeredthe assembly of a ribosomal translational complex. Proteins destinedfor passage through the membrane system are equipped with a “signalsequence” at the N (for amino) terminal end of the polylpeptide chain,which is the first part to be synthesized.
The appearance of the signalsequence halts further synthesis. For protein synthesis to resume thesignal sequence must become associated with the surface of the endoplasmic reticulum, specifically with “docking proteins” embedded in theER membrane. While the presence of a signal sequence may be said tobe encoded in DNA, its function can be realized only in the context ofa receptor complex already present in the ER. These receptors themselveswould be “coded for” with signal sequences, and yet they must alwaysbe dependent on the presence of receptors already being embedded inthe ER in order to receive them.In a pattern that will be shown to be more elaborate, the differentiatedstructure of the membrane system constitutes the template for its ownrenewal. Genetically coded target information is only meaningful in thecontext of the already existing template of the differentiated membranesystem which interprets it.
Passage from the endoplasmic reticulum to thecis golgi and from one pancake in the stack to the next occurs by way oftransient transport vesicles. Small vesicles with specific contents “budoff” from the ends of the pancakes, only to fuse with the next pancake inthe stack.
In this way there is a steady flow of membrane directed outwardtoward the plasma membrane. Proteins to be secreted outside the cell arefirst deposited within the endoplasmic reticular lumen and then progres-A Critique of Pure (Genetic) Information83sively transported by one vesicle after another until fusion with theplasma membrane excretes them into the extracellular environment.
Proteins destined for inclusion in a certain membrane become embedded inthe endoplasmic reticulum membrane; then, within the membranes aretransported by way of each of the successive transport vesicles. Transportvesicles are each limited to communication between two levels, i.e., twopancakes. A class of recognition proteins referred to as SNARES (solubleNSF attachment protein receptor) largely mediates specificity of transportfunction. These are subdivided into the receptors which are present in thevesicle, referred to as v-SNARES, and those in the target pancake referrred to as t-SNARES (Rothman & Weiland 1996). As in the case of thedocking proteins of the ER, t-SNARES must be present in the specifictarget membranes, marking the different “addresses” at each sequentiallevel, for the continued self-renewing cellular assembly to proceed.
Thedifferentiated distribution of receptors in the membranous compartmentsof the cell are preserved through cell division, in perpetuity, for all succeeding members of the cellular lineage. (Only from cellular order comescellular order.) Newly synthesized proteins embarking on their transitthrough the membranous system of the cell are endowed with endogenoussorting signals that most often consist of 4 to 25 residues but may also bedetermined by three-dimensional conformation (Rothman & Weiland1996).
Endogenous signals may either specify association with a vSNARE and thus inclusion in a nascent transport vesicle and transit to thenext locale, or they may serve to restrict inclusion, possibly by leading toassociation with membranous regions or patches that are refractory toinclusion in a transport vesicle. The conditions for retention are also likelyto be differentiated features of the particular membrane location(pancake) which must be preserved and passed on across cell divisionsand organismic generations.
Proteins that lack any specific transit signalwill simply travel by bulk flow according to its concentration in the donorcompartment.The movement of selected components from out of a membranouscompartment (pancake) begins with the attachment of “coat proteins”to the outer (cytoplasmic) side of one region of the pancake. (This is howthe budding off of a transport vescicle begins.) The coat proteins arerecruited from the cytoplasm and consist of repeated units of the same84Chapter 3protein that ultimately form a spherical shell around the emerging vesiclemembrane.
The v-SNARES that will direct the vesicle to its next compartment after it buds off the “donor” pancake become concentrated inthat region surrounded by coat protein, as do other transiting proteinswhich contain the appropriate signals.The mechanics of budding off are realized through the effects of thecoat proteins whose polymerization on the membrane surface results inforcing it into a kind of droplet that can close unto itself as a sphere andbecome released.
Assembly of cell surface-coat proteins requires the useof cellular energy stores by way of the degradation of high-energy guanosine triphosphate (GTP) molecules. Movement of the new vesicle to thenext compartment generally depends on diffusion alone (This is not thecase for the transport of synaptic vesicles carrying neurotransmitterswhere microtubule tracks are deployed.) Specificity of contact is providedby the recognition reactions between the v-SNARES on the vesicle andthe t-SNARES on the target pancake. The fusion of vesicle with targetmembrane is thermodynamically unfavorable.
The energy barrier tospontaneous fusions protects the highly differentiated and informationrich membrane system of the cell from entropic heat decay within thattemperature range which is compatible with the life of the organism.Fusion of the vesicle with its target compartment membrane requires therelease of coat proteins from the vesicle, the achievement of close apposition of membranes mediated by the specific binding of SNARES,the formation of a new complex of proteins including NSF (Nethylmaleimide-sensitive fusion protein), and soluble NSF attachmentprotein (SNAP), which together mediate the fusion process. Realizationof the fusion event requires the expenditure of cellular energy stores, thistime in the form of adenosine triphosphate (ATP), the principal highenergy intermediate that serves as the common coin of cellular energetics.
After fusion with a new compartment the contents of the vesiclebecome disseminated. The new compartment will then undergo its owntransport vesicle formation in which a different (albeit overlapping) setof proteins will become enclosed according to the specific biochemicalidentity of that compartment.Schrödinger’s reflections on the requirement of heritable order lackedany conception of how fluid structures such as membranes could resistA Critique of Pure (Genetic) Information85entropic heat decay. That the dynamics and renewal of cellular membrane systems and other structural systems require a constant expenditure of cellular energy provides a strong indication of the extent to whichthese systems are principal sources of biological order and informationunto themselves. Recognition of the self-templating, highly differentiated, decay-resisting, far-from-equilibrium nature of the membranesystem, as well as other organizational structures, should be of no smallsignificance in reconsidering Schrödinger’s argument for why a hereditary code-script had to be the self-executing governor of all cellularorganismal processes.The system of membranous bodies described as being biochemicallydistinct is also functionally differentiated.
Each level in the stack has specific biosynthetic capacities. I have already argued that the biological“meaning” of a protein is not realized simply at the level of its aminoacid sequence but is dependent on its localization in a particular cellular, or extracellular, compartment or milieu. In addition, the biochemical and cellular significance of a protein is highly affected by itspost-translational modification, i.e., its acquisition of additional covalentbonds to carbohydrates, lipids, phosphate groups, and so on. Extendingoutward from the surface of all cells is a corona of mixed and variablycharged oligosaccharide chains and proteoglycans, generally referredto as the “glycocalyx.” The processes of multicellular development anddifferentiation—that is, organismic ontogeny—entails dynamic interactions between cells which result in the induction of new cell states (andsometimes cell death), in cell proliferation, as well as in the reproductivequiescence and stabilization of induced states during the formation oftissues.The glycocalyx is critically involved in the “sociality” of cellular development.
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