(CB) CH 12

SNARE

According to the SNARE hypothesis, the proper sorting and targeting of vesicles in eukaryotic cells involves two families of ______

coat proteins

After formation of a free vesicle, hydrolysis of GTP leads to the release of _____ _______ for another cycle of vesicle budding

desensitization

As EGF receptors are internalized, the cell becomes less responsive to EGF, a process known as ________.

autophagic digestion

As a red blood cell matures, virtually all of the intracellular content is destroyed, including all of the mitochondria. This destruction is accomplished by _________ ________

digested

As early endosomes fuse with vesicles from the TGN containing acid hydrolases, they mature to form late endosomes and lysosomes, in which the ingested material is _____

TGN

As we have seen, the final sorting of proteins synthesized in the ER occurs in the ______ when lipids and proteins are packaged into vesicles for transport to various destinations.

ARF

Assembly of a COPI coat is mediated by ______. In the cytosol, _______ occurs as part of an _____-GDP complex.

auto

Because circulating LDL cannot be detected in such patients, the _______-regulatory pathway for cholesterol synthesis is not activated. As a result, those with FH continue to make cholesterol and sustain high circulating LDL and cholesterol levels.

endomembrane system

Components of the ___________ ___________

endocytosis

General steps of _______________: 1 small segment of the plasma membrane progressively folds inward 2 pinches off to form an endocytic vesicle containing ingested substances or particles.

LDL receptor

In individuals with FH, mutations in the ___ _________ gene can result in receptors that are unable to bind circulating lipoproteins or can cause the absence of the LDL receptor.

fusion

NSF and SNAPs are involved in ______ between a variety of cellular membranes, indicating they are not responsible for specificity during targeting.

vesicle.

Once firmly anchored, ARF binds to COPI multimers, and assembly of the coat drives the formation and budding of a new __________

degradation

One of the most important functions of lysosomal enzymes is the __________ of foreign material brought into eukaryotic cells by phagocytosis and receptor-mediated endocytosis

transport vesicle

Rab GTPase are found connected to the _______ membrane

tethering proteins

Since the discovery of SNARE proteins, it has become clear that they alone cannot account for the specificity observed in vesicle targeting. A distinct class of proteins known as ______ _______ acts over longer distances and provides specificity by connecting vesicles to their target membranes prior to v-SNARE/t-SNARE interaction

tethering

Step 1 in the snare hypothesis is the proper vesicle is recognized and bound by particular membrane-anchored ______ proteins

Rab GTPase

Step 2 in the SNARE hypothesis is that a _____ _____ bound to the incoming vesicle stimulates association of v-SNARE with t-SNARE

membrane fusion

Step 3 of SNARE hypothesis is ______ _________ promoted by the interaction between v-SNARE and t-SNARE

dissociation

Step 4 is the binding of NSF and SNAPs promotes ________ of the SNARE complex

exocytosis

Steps of ______: 1) Vesicle fuses with plasma membrane 2) Combo discharges the vesicle contents outside of the cell 3) Vesicle membrane becomes integrated into the plasma membrane. Note that the inner surface of the vesicle becomes the outer surface of the plasma membrane

COPII

The ________ coat found in yeast is assembled from two protein complexes—called Sec13/31 and Sec23/24—and a small GTP-binding protein called SarI, which is similar to ARF

vesicles

The basic molecular components that mediate sorting and targeting of ________ in eukaryotic cells include tethering proteins, v-SNAREs on transport vesicles, t-SNAREs on target membranes, Rab GTPase, NSF, and several SNAPs.

autophagy

The digestion of old or unwanted organelles or other cell structures is called ___________, which is Greek for "self-eating"

activation

The final step in lysosome development is the __________ of the acid hydrolases, which occurs as the enzymes and their substrates encounter a more acidic environment.

exocytosis

The general function of_____________ is to release contents outside of the cell. Also leads to plasma membrane build up

microtubule tracks

The mechanism of the underlying movement of exocytotic vesicles is ________ _________

GTP

The release of coat proteins is triggered by ____ hydrolysis

ARF

The role of _____ (a small GTP binding protein) helps assemble the COPI coat. The ARF-GTP complex is hydrolyzed which induces conformational change and AFR can attach to the lipid bilayer.

AP

There are slightly different _____ complexes that bind to different transmembrane receptor proteins and confer specificity during vesicle budding and targeting

acidic

There are two ways that acid hydrolases can be activated by finding more _______ environments 1) ATP-dependent proton pumps 2) Fusion with existing lysosome

statins

Treatments include ________ which inhibit an enzyme called HMG-CoA reductase which is synthesized in the liver.

adaptin subunits

When clathrin-coated vesicles form from the TGN, ______ _______, of the the adaptor complexes, are partly responsible for the specificity displayed when receptors are concentration for inclusion in a budding vesicle

extracellular digestion

Whereas most digestive processes involving lysosomal enzymes occur intracellularly, in some cases lysosomes discharge their enzymes to the outside of the cell by exocytosis, resulting in ________ _______

t

___-SNAREs are found on the _________ membrane

v

___-SNAREs are found on transport vesicles

lysosome

___: an organelle of the endo-membrane system that contains digestive enzymes * isolate digestive enzymes from the rest of the cell * digest materials brought in by endocytosis + intracellular waste

AP Complexes

______ _____: protein complexes found along with clathrin in the coats of clathrin-coated vesicles * promote the assembly of clathrin coats * euk cells contain at least four types of AP complexes

coated pits

______ ______ serve as sites for the collection and internalization of receptor-ligand complexes

early endosomes

______ _________ are formed by the coalescence of vesicles from the TGN and vesicles from the plasma membrane.

SNARE

______ hypothesis: model explaining how membrane vesicles fuse with the proper target membrane

EGF

______ is a variation of receptor mediated endocytosis. * stimulates division of epithelial cells.

autophagic

______ vacuole: the valcuole that is a product of macrophagy

COPII

______-coated vesicles: involves in the transport of material from the ER to the golgi apparatus.

transcytosis

______: endocytosis of material into vesicles that move to the opposite side of the cell and fuse with the plasma membrane, releasing the material into the extracellular space

Phagocytic vacuoles

_______ ______ are transformed into lysosomes by fusing with early endosomes * can vary in size, appearance, content, and digestion

Soluble

_______ products of digestion, such as sugars, amino acids, and nucleotides, are then transported across the lysosomal membrane into the cytosol and are used as a source of nutrients by the cell.

COPI

_______-coated vesicles: facilitate retrograde transport of proteins from the folfi back to the ER, as well as between the cisternae of the golgi apparatus

SNARE

________ proteins mediate fusion between vesicles and target membranes

clathrin

________ was required for promoting membrane curvature and invagination of the coated pits

microphagy

________: process by which small bits of cytoplasm are surrounded by ER membrane to form an autophagic vesicle whose contents are then digested either by accumulation of lysosomal enzymes or by fusion of the vesicle with a late endosome.

COPI

_________-coated vesicles are surrounded by coats composed of COPI protein and ADP ribosylation factor (ARF), a small GTP-binding protein

COPI

_________-coated vesicles: are involved in retrograde transport from the Golgi apparatus back to the ER as well as bidirectional transport between Golgi apparatus cisternae.

Clathrin

_________-coated vesicles: involved in the selective transport of proteins from the TGN to the endosomes and in the endocytosis of receptor-ligand complexes from the plasma membrane

Dynamin

_________: cytosolic GTPase required for coated pit constriction and closing of a budding, clathrin-coated vesicle * temperature shift that disrupts the dynamin leads to instant paralyzing * as GTP is hydrolyzed the dynamin rinds righten and separate the fully sealed endocytic vesicle from the plasma membrane

macrophagy:

_________: process by which an organelle becomes wrapped in a double membrane derived from the endoplasmic reticulum, creating an autophagic vacuole that acquires lysosomal enzymes which degrade the organelle.

golgins

__________ one of a class of tethering proteins that connect vesicles to the Golgi and Golgi cisternae to each other. * also important in connecting Golgi cisternae to one other * evidence: antibodies sent after golgins lead to disruption of structure of the golgi mediated cisternae

triskelions

__________ surrounds clathrin-coated vesicles and forms protein lattices. * help flat membranes form spherical vesicles * overlapping triskelions form overlapping networks that confer mechanical strength

Deficiencies

___________ in desensitization caused by defective endocytosis can lead to overstimulation by EGF, resulting in excessive cell growth, cell division, and possible tumor formation.

peroxisome

___________: single membrane-bounded organelle that contains catalase and one or more hydrogen peroxide-generating oxidases and is therefore involved in the metabolism of hydrogen peroxide.

constitutive

____________ secretion: "continuous/independent default pathways". * Many nonspecific proteins use this type of secretion. Removal of the KDEL retrieval tag leads to use of this. Amino acid sequences may ID specific proteins for constitutive secretion. * EX is the release of mucus by cells that line your intestine.

Secretory vesicle

_____________ ____________: membrane bounded compartments of eukaryotic cells that carry secretory proteins from the golgi apparatus to the plasma membrane for exocytosis * may serve as a storage compartment for such proteins before they are released * Large dense vesicles are known as secretory granules

Polarized secretions

_____________ secretion : "secretion that occurs only on a specific surface of the cell" * Ex nerve cells that secrete NT at junctions

Regulated

_____________ secretion: "accumulated and then released in response to specific triggers." * start as immature secretory vesicles which undergo subsequent maturation. Maturation is related to the increased concentration of proteins. * zymogen granules: a type of mature regulated secretory vesicle that are large and contain highly concentrated protein. * Ex release of neurotransmitters, insulin from pancreas, zymogens from pancreatic cells

COPII

_____________: main protein component of COPII-coated vesicles, which are involved in transport from the ER to the Golgi apparatus.

fluid-phase

______________ is a type of pinocytosis for nonspecific internalization of extracellular fluid * proceeds at a relatively constant rate * controls a cell volume and surface area fluid-phase * endocytic vesicles, like clathrin-dependent endocytic vesicles, are routed to early endosomes.

triskelion

each _________ is composed of 3 clathrin heavy chains and 3 clathrin light chains. the assembly of these tri-skeleton molecules form characteristic pentagons and hexagons

ARF-GTP

fungal toxin brefeldin A, which inhibits this process by interfering with the ability of the guanine nucleotide exchange factor to produce _____-____ from ARF-GDP.

ARF

guanine nucleotide exchange factor initiates the mechanism for attachment of ______ to the lipid bilayer. Steps include: - encountering said molecule - GTP hydrolysis which induces conformational change - exposed hydrophobic N-terminus - attachment into lipid bilayer membrane

indigestible

lysosomal storage diseases are usually characterized by the accumulation of _________ material

autophagic

mature lysosomes containing materials of intracellular origin are known as _________ lysosomes

heterophagic

mature lysosomes containing substances of extracellular origin are known as ________ lysosomes

residual body

only indigestible material remains in the lysosome, which becomes a _______ _______ as digestion ceases * protozoa spit out this debris * vertebrates cannot spit it out. this can lead to cell aging or cell death. * neutrophils can "educate" immune system with this debris

clathrin-dependent

receptor-mediated (_________-_________) endocytosis: type of endocytosis initiated at coated pits and resulting in coated vesicles; * major mechanism for selective uptake of macromolecules and peptide hormones

lysosomal enzyme

steps of _______ ________ synthesis 1 ribosome on RER 2 translocated through pore in ER membrane into ER lumen 3 transport to golgi apparatus 4 addition of tag 5 packaging in clathrin-coated vesicles

late endosome

the early endosome matures to form a ________ ________, an organelle having a full complement of acid hydrolases but not engaged in digestive activity.

SNARE

two families of proteins involved in targeting and sorting membrane vesicles; * v-SNARES found on transport vesicles * t-SNARES found on target membranes