页数：44页文件大小：1.20 MB来源： 分子生物学基因Geneppt课件
本课件为《分子生物学》第25章蛋白质转运（Protein trafficking），依据 Gene VII 教材编排，沿Oligosaccharides等小节推进，讲解本章核心概念与分子机制，配逐页图示与文字版。
Chapter 25 Protein trafficking
Sorting signal is a motif in a protein (either a short sequence of amino acids or a covalent modification) that is required for it to be incorporated into vesicles that carry it to a specific destin at ion.
Figure 25.1 Proteins that enter the endoplasmic reticulum are transported to the Golgi and towards the plasma membrane. Specific signals cause proteins to be returned from the Golgi to the ER, to be retained in the Golgi, to be retained in the plasma membrane, or to be transported to endosomes and lysosomes. Proteins may be transported between the plasma membrane and endosomes.
Figure 25.2 Vesicles are released when they bud from a donor compartment and are surrounded by coat proteins (left). During fusion, the coated vesicle binds to a target compartment, is uncoated, and fuses with the target membrane, releasing its contents (right).
Figure 25.3 An oligosaccharide is formed on dolichol and transferred by glycosyl transferase to asparagine of a target protein.
Figure 25.4 Sugars are removed in the ER in a fixed order, initially comprising 3 glucose and 1-4 mannose residues. This trimming generates a high mannose oligosaccharide.
Figure 25.5 Processing for a complex oligosaccharide occurs in the Golgi and trims the original pre formed unit to the inner core consisting of 2 N-acetyl-glucos a mine and 3 mannose residues. Then further sugars can be added, in the order in which the transfer enzymes are encountered, to generate a terminal region containing N-acetyl-glucos a mine, galactose, and sialic acid.
Figure 25.6 The Golgi apparatus consists of a series of individual membrane stacks. Photograph kindly provided by Alain Rambourg.
Figure 25.7 A Golgi stack consists of a series of cisternae, organized with cis to trans polarity. Protein modific at ions occur in order as a protein moves from the cis face to the trans face.
Figure 25.8 Proteins are transported in coated vesicles. Constitutive (bulk flow) transport from ER through the Golgi takes place by COP-coated vesicles. Clathrin-coated vesicles are used for both regulated exocytosis and endocytosis.
Figure 25.9 Coated vesicles are released from the trans face of the Golgi. The diameter of a vesicle is ~70 nm. Photograph kindly provided by Lelio Orci.
Figure 25.2 Vesicles are released when they bud from a donor compartment and are surrounded by coat proteins (left). During fusion, the coated vesicle binds to a target compartment, is uncoated, and fuses with the target membrane, releasing its contents (right).
Figure 25.10 Vesicle formation results when coat proteins bind to a membrane, deform it, and ultimately surround a membrane vesicle that is pinched off.
Endocytic vesicles are membranous particles that transport proteins through endocytosis; also known as clathrin-coated vesicles.
Figure 25.11 Coated vesicles have a polyhedral lattice on the surface, created by triskelions of clathrin. Photograph kindly provided by Tom Kirchhausen.
Figure 25.12 Clathrin-coated vesicles have a coat consisting of two layers: the outer layer is formed by clathrin, and the inner layer is formed by adaptors, which lie between clathrin and the integral membrane proteins.
Are coated vesicles responsible for all transport between membranous systems? There are conflicting models for the nature of forward transport from the ER, through Golgi cisternae, and then from the TGN to the plasma membrane.
Figure 25.13 ARF and coa to mer are sufficient for the budding of COP-I-coated vesicles.
Figure 25.14 Vesicle uncoating is triggered by hydrolysis of GTP bound to ARF.
Figure 25.15 Specificity for docking is provided by SNAREs. The v-SNARE carried by the vesicle binds to the t-SNARE on the plasma membrane to form a SNAREpin. NSF and SNAP remain bound to the far end of the SNAREpin during fusion. After fusion, ATP is hydrolyzed and NSF and SNAP dissociate to release the SNAREs.
Figure 25.16 A SNAREpin forms by a 4-helix bundle. Photograph kindly provided by Axel Brunger.
Figure 25.17 A SNAREpin complex protrudes parallel to the plane of the membrane. An electron micrograph of the complex is superimposed on the model. Photograph kindly provided by James Rothman.
Figure 25.18 Neurotransmitters are released from a donor (pre synaptic) cell when an impulse causes exocytosis. Synaptic (coated) vesicles fuse with the plasma membrane, and release their contents into the extracellular fluid.
Figure 25.19 The kiss and run model proposes that a synaptic vesicle touches the plasma membrane transiently, releases its contents through a pore, and then reforms.
Figure 25.20 When synaptic vesicles fuse with the plasma membrane, their components are retrieved by endocytosis of clathrin-coated vesicles.
Figure 25.21 Rab proteins affect particular stages of vesicular transport.
Lysosomes are small bodies, enclosed by membranes, that contain hydrolytic enzymes in eukaryotic cells.
Figure 25.22 A transport signal in a trans-membrane cargo protein interacts with an adaptor protein.
Figure 25.23 A transport signal in a luminal cargo protein interacts with a transmembrane receptor that interacts with an adaptor protein.
Figure 25.5 Processing for a complex oligosaccharide occurs in the Golgi and trims the original pre formed unit to the inner core consisting of 2 N-acetyl-glucos a mine and 3 mannose residues. Then further sugars can be added, in the order in which the transfer enzymes are encountered, to generate a terminal region containing N-acetyl-glucos a mine, galactose, and sialic acid.
Figure 25.24 An (artificial) protein containing both lysosome and ER-targeting signals reveals a pathway for ER-localiz at ion. The protein becomes exposed to the first but not to the second of the enzymes that generates mannose-6-phosphate in the Golgi, after which the KDEL sequence causes it to be returned to the ER.
Figure 25.24 An (artificial) protein containing both lysosome and ER-targeting signals reveals a pathway for ER-localiz at ion. The protein becomes exposed to the first but not to the second of the enzymes that generates mannose-6-phosphate in the Golgi, after which the KDEL sequence causes it to be returned to the ER.
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Figure 25.25 Endosomes sort proteins that have been endocytosed and provide one route to the lysosome. Proteins are transported via clathrin-coated vesicles from the plasma membrane to the early endosome, and may then either return to the plasma membrane or proceed further to late endosomes and lysosomes. Newly synthesized proteins may be directed to late endosomes (and then to lysosomes) from the Golgi stacks. The common signal in lysosomal targeting is the recognition of mannose-6-phosphate by a specific receptor.
Figure 25.25 Endosomes sort proteins that have been endocytosed and provide one route to the lysosome. Proteins are transported via clathrin-coated vesicles from the plasma membrane to the early endosome, and may then either return to the plasma membrane or proceed further to late endosomes and lysosomes. Newly synthesized proteins may be directed to late endosomes (and then to lysosomes) from the Golgi stacks. The common signal in lysosomal targeting is the recognition of mannose-6-phosphate by a specific receptor.
说明：本页源文与上一页完全相同，疑为课件连续两页沿用同一页内容，已按原文保留。
Figure 25.26 LDL receptor transports apo-B (and apo-E) into endosomes, where receptor and ligand separate. The receptor recycles to the surface, apo-B (or apo-E) continues to the lysosome and is degraded, and cholesterol is released.
Figure 25.27 Transferrin receptor bound to transferrin carrying iron releases the iron in the endosome; the receptor now bound to apo-transferr in (lacking iron) recycles to the surface, where receptor and ligand dissociate.
Figure 25.28 EGF receptor carries EGF to the lysosome where both the receptor and ligand are degraded.
Figure 25.29 Ig receptor transports immunoglobulin across the cell from one surface to the other.
Figure 25.12 Clathrin-coated vesicles have a coat consisting of two layers: the outer layer is formed by clathrin, and the inner layer is formed by adaptors, which lie between clathrin and the integral membrane proteins.
Figure 25.30 The cytoplasmic domain of an internalized receptor interacts with proteins of the inner layer of a coated pit.
1.Proteins that reside within the reticuloendothelial system or that are secreted from the plasma membrane enter the ER by cotranslational transfer directly from the ribosome. 2.Proteins are transported between membranous surfaces as cargoes in membrane-bound coated vesicles. 3.Modification of proteins by addition of a pre formed oligosaccharide starts in the endoplasmic reticulum. 4.Different types of vesicles are responsible for transport to and from different membrane systems. 5.COP-I-coated vesicles are responsible for retrograde transport from the Golgi to the ER. 6.COP-II vesicles undertake forward movement from the ER to Golgi.
7.In the pathway for regulated secretion of proteins, proteins are sorted into clathrin-coated vesicles at the Golgi trans face. 8.Budding and fusion of all types of vesicles is controlled by a small GTP-binding protein. 9.Vesicles recognize appropriate target membranes because a vSNARE on the vesicle pairs specifically with a tSNARE on the target membrane. 10.Receptors may be internalized either continuously or as the result of binding to an extracellular ligand. 11.The acid environment of the endosome causes some receptors to release their ligands; the ligand are carried to lysosomes, where they are degraded, and the receptors are recycled back to the plasma membrane by means of coated vesicles.
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